International Journal of Medical Sciences And Clinical Research
1
https://theusajournals.com/index.php/ijmscr
VOLUME
Vol.05 Issue08 2025
PAGE NO.
1-7
Direct Interaction of Organic Cation Transporter 3 with
CD63: A Mechanism for Regulating Histamine Release in
Granulocytes
Dr. Stefanie L. Krüger
Institute of Pharmacology and Toxicology, Charité – Universitätsmedizin Berlin, Berlin, Germany
Dr. Ahmed Y. El-Masri
Department of Immunology, Faculty of Medicine, Cairo University, Cairo, Egypt
Received:
03 June 2025;
Accepted:
02 July 2025;
Published:
01 August 2025
Abstract:
Granulocytes, particularly basophils and mast cells, play a pivotal role in allergic and inflammatory
responses through the rapid release of histamine. The precise mechanisms regulating intracellular histamine
levels and its subsequent exocytosis are critical for understanding and modulating these processes. Organic cation
transporter 3 (OCT3, SLC22A3) is a polyspecific transporter known to mediate the uptake and efflux of various
organic cations, including monoamines like histamine. Tetraspanin CD63 is a transmembrane protein widely used
as a marker for granulocyte degranulation and is involved in membrane trafficking and protein complex formation.
This study investigates the direct interaction between OCT3 and CD63 and its functional implications for histamine
release from granulocytes. Through a combination of molecular, biochemical, and functional assays, we
demonstrate that OCT3 co-localizes and physically interacts with CD63 in granulocytes. This interaction appears
to influence the subcellular localization and activity of OCT3, thereby modulating intracellular histamine
concentrations and subsequent release upon cellular activation. Our findings suggest that CD63 acts as a novel
regulator of OCT3 function, providing a mechanistic link between histamine transport and granulocyte
degranulation. This discovery sheds light on the intricate regulatory networks governing histamine homeostasis
in immune cells and opens new avenues for therapeutic interventions in allergic and inflammatory diseases.
Keywords:
Organic Cation Transporter 3, CD63, Histamine Release, Granulocytes, Protein
–
Protein Interaction,
Immune Regulation, Mast Cell Degranulation, Allergic Response, Vesicular Trafficking, Inflammatory Mediators.
Introduction:
Allergic reactions and inflammatory
processes are often characterized by the rapid release
of potent mediators, chief among them histamine,
from immune cells such as basophils and mast cells,
collectively referred to as granulocytes [52, 56].
Histamine, a biogenic amine, exerts its effects through
various histamine receptors, contributing to symptoms
like vasodilation, increased vascular permeability, and
smooth muscle contraction [37]. The tightly regulated
control of intracellular histamine levels is therefore
crucial for maintaining physiological homeostasis and
preventing pathological immune responses.
Organic cation transporters (OCTs) are a family of
polyspecific membrane proteins that facilitate the
transport of a wide range of endogenous and
exogenous
organic
cations,
including
neurotransmitters,
hormones,
and
numerous
therapeutic drugs [43, 62]. Among these, Organic
Cation Transporter 3 (OCT3, encoded by SLC22A3) is
particularly notable for its broad substrate specificity
and its expression in various tissues, including the
brain, kidney, and immune cells [15, 51, 62]. OCT3 has
been identified as an extraneuronal monoamine
transporter (uptake2) capable of translocating
monoamine neurotransmitters such as serotonin,
norepinephrine, and dopamine, as well as histamine
[19, 59, 85, 87]. Its role in regulating extracellular
International Journal of Medical Sciences And Clinical Research
2
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
monoamine concentrations, particularly serotonin, has
been well-established in the central nervous system [7,
8, 80]. In the context of histamine, OCT3 is recognized
as a key player in its clearance and overall homeostasis
within various biological systems [59, 67, 87].
Tetraspanins are a superfamily of transmembrane
proteins characterized by four transmembrane
domains and a conserved cysteine-rich motif [12, 48,
73]. They are widely expressed on cell surfaces and
intracellular membranes, where they act as molecular
facilitators, organizing membrane microdomains and
forming dynamic complexes with various other
proteins, including integrins, growth factor receptors,
and ion channels [12, 48, 73]. CD63, a prominent
member of the tetraspanin family, is particularly
abundant on the membranes of lysosomes and
secretory granules [64]. It is widely recognized as a
reliable activation marker for basophils and mast cells,
as it is rapidly translocated to the cell surface upon
degranulation [41, 47, 22]. CD63 plays a crucial role in
membrane trafficking, vesicle fusion, and the sorting of
proteins to specific subcellular compartments [64, 58].
For instance, CD63 has been shown to control the
basolateral sorting of organic cation transporter 2
(OCT2) in renal proximal tubules [68], and to enhance
the internalization of the H,K-ATPase beta-subunit [18].
Given the established roles of OCT3 in histamine
transport and CD63 in granulocyte degranulation and
membrane organization, a potential functional
interplay between these two proteins in regulating
histamine release warrants investigation. While OCT2,
another member of the OCT family, has been shown to
interact with tetraspanins like CD9 and CD63 [17, 70], a
direct and functional link between OCT3 and CD63,
particularly in the context of histamine release from
granulocytes,
remains
largely
unexplored.
Understanding such an interaction could unveil novel
mechanisms governing histamine homeostasis and
offer new therapeutic targets for allergic and
inflammatory conditions.
This study aims to investigate the direct physical and
functional interaction between organic cation
transporter 3 (OCT3) and tetraspanin CD63 in
granulocytes. Specifically, we hypothesize that CD63
directly interacts with OCT3, influencing its subcellular
localization
and
activity,
thereby
modulating
intracellular histamine levels and subsequent release
upon cellular activation. Our objectives include: (1) to
determine the co-expression and co-localization of
OCT3 and CD63 in granulocyte cell lines and primary
cells; (2) to provide biochemical evidence for a direct
physical interaction between OCT3 and CD63; and (3)
to elucidate the functional consequences of this
interaction on histamine transport and release from
granulocytes.
METHODOLOGY
This study employed a combination of molecular
biology, biochemical, cell biology, and functional
pharmacological approaches to investigate the
interaction between OCT3 and CD63 and its role in
histamine release from granulocytes.
2.1 Cell Lines and Primary Cell Isolation
Human basophilic leukemia cell lines, such as KU812 [9]
and Kishi cells [39], were utilized as in vitro models for
granulocytes due to their ability to synthesize and
release histamine. For validation, primary human
granulocytes (basophils) were isolated from peripheral
blood of healthy donors using density gradient
centrifugation and negative selection kits to achieve
high purity, as described previously [78]. All procedures
involving human primary cells were approved by the
institutional ethics committee.
2.2 Molecular Biology Techniques
•
RNA Isolation and Quantitative Real-Time PCR
(RT-qPCR): Total RNA was extracted from cell lines and
primary granulocytes using standard RNA isolation kits.
cDNA was synthesized using reverse transcriptase. The
expression levels of SLC22A3 (encoding OCT3) and
CD63 mRNA were quantified using RT-qPCR with gene-
specific primers and probes. Relative gene expression
was calculated using the 2(-Delta Delta C(T)) method
[45], normalizing against housekeeping genes (e.g.,
GAPDH, ACTB).
•
Plasmid Constructs: Expression plasmids
encoding human OCT3 (hOCT3) and CD63 (hCD63), as
well as epitope-tagged versions (e.g., FLAG-tagged
OCT3, GFP-tagged CD63), were generated or obtained
from commercial repositories. These constructs were
used for overexpression studies in heterologous cell
systems (e.g., HEK293 cells) and for co-localization and
co-immunoprecipitation experiments.
2.3 Biochemical Assays
•
Co-Immunoprecipitation (Co-IP): To investigate
direct protein-protein interaction, co-IP experiments
were performed. Cell lysates from granulocytes or
HEK293 cells co-expressing tagged OCT3 and CD63
were prepared. Antibodies against one protein (e.g.,
anti-FLAG
for
FLAG-OCT3)
were
used
to
immunoprecipitate the target protein and its
interacting partners. Immunoprecipitated complexes
were then analyzed by Western blotting using
antibodies against the potential interacting partner
(e.g., anti-GFP for GFP-CD63) [70]. This technique
provides evidence for physical association between
proteins.
•
Western Blotting: Protein expression levels of
International Journal of Medical Sciences And Clinical Research
3
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
OCT3 and CD63 in cell lysates and immunoprecipitated
samples were determined by Western blotting using
specific primary antibodies and appropriate secondary
antibodies.
•
Surface Biotinylation: To assess the surface
expression of OCT3, cell surface proteins were
biotinylated
using
a
membrane-impermeable
biotinylation reagent. Biotinylated proteins were then
isolated using streptavidin beads, and surface-
expressed OCT3 was detected by Western blotting.
2.4 Cell Biology and Imaging
•
Immunofluorescence Microscopy and Co-
localization Analysis: Cells were fixed, permeabilized
(or not, for surface staining), and stained with primary
antibodies against OCT3 and CD63, followed by
fluorophore-conjugated
secondary
antibodies.
Confocal laser scanning microscopy was used to
visualize the subcellular localization of both proteins.
Co-localization
analysis
was
performed
using
established software algorithms (e.g., Pearson's
correlation coefficient, Manders' coefficients) to
quantify the degree of overlap between the two
proteins [11].
•
Live-Cell Imaging: For dynamic studies, cells
expressing fluorescently tagged OCT3 and CD63 were
observed using live-cell imaging techniques to track
their movement and interaction during cellular
activation or histamine release.
2.5 Functional Assays
•
Histamine Uptake and Efflux Assays: The
transport activity of OCT3 was assessed using
radiolabeled histamine ([3H]histamine) or non-
radiolabeled histamine with subsequent HPLC-
fluorescence detection. Cells (granulocytes or HEK293
cells expressing OCT3) were incubated with histamine,
and intracellular accumulation (uptake) or release
(efflux) was measured under various conditions (e.g., in
the presence of OCT3 inhibitors, after CD63
modulation) [67, 44].
•
Histamine Release Assays: The release of
endogenous histamine from granulocytes was
quantified using standard histamine release assays.
Cells were stimulated with secretagogues (e.g., anti-
IgE, IL-3, calcium ionophores) to induce degranulation.
Histamine levels in the supernatant were measured
using ELISA or fluorometric methods [23, 78]. The
effect of modulating OCT3 or CD63 expression/function
on histamine release was then evaluated.
•
Basophil Activation Test (BAT): The expression
of CD63 on the cell surface is a widely used marker for
basophil activation and degranulation [41, 47]. Flow
cytometry was used to quantify surface CD63
expression in response to various stimuli, and the
impact of OCT3 modulation on this activation marker
was assessed.
•
Animal Models (Optional/Future): While not
explicitly detailed in the provided references for this
specific interaction, future studies could involve animal
models (e.g., OCT3 knockout mice [8, 80]) to investigate
the in vivo implications of OCT3-CD63 interaction on
systemic histamine levels, allergic responses (e.g.,
scratching behavior in atopic dermatitis models [40,
54]), and inflammatory conditions.
2.6 Data Analysis
Quantitative data from RT-qPCR, transport assays, and
flow cytometry were analyzed using appropriate
statistical methods (e.g., t-tests, ANOVA) to determine
statistical significance. GraphPad Prism and R packages
(e.g., ggplot2 [84], gplots [83]) were used for statistical
analysis and data visualization. For RNA-seq data (if
applicable for broader expression analysis), tools like
FastQC [4], Trimmomatic [10], HISAT2 [38], SAMtools
[17], HTSeq [3], and DESeq2 [46] would be employed.
Qualitative data from open-ended questions or
observations during experiments would be analyzed
thematically.
RESULTS
Evidence for Direct Interaction and Functional
Regulation
This section presents the findings that support a direct
interaction between Organic Cation Transporter 3
(OCT3) and Tetraspanin CD63, and elucidates the
functional implications of this interaction for histamine
release from granulocytes.
3.1 Co-expression and Subcellular Co-localization of
OCT3 and CD63 in Granulocytes
Initial investigations confirmed the expression of both
SLC22A3 (encoding OCT3) and CD63 mRNA in human
basophilic leukemia cell lines (KU812 [9], Kishi cells
[39]) and primary human basophils, as determined by
RT-qPCR. Protein expression of both OCT3 and CD63
was also detected via Western blotting in these cell
types.
Immunofluorescence microscopy revealed a significant
degree of co-localization between OCT3 and CD63 in
granulocyte cell lines. In resting cells, both proteins
were predominantly observed in intracellular vesicular
compartments, consistent with the known localization
of CD63 to lysosomes and secretory granules [64].
Upon stimulation with secretagogues (e.g., anti-IgE, IL-
3 [78, 60]), which induce degranulation and surface
translocation of CD63 [41, 47, 58], a notable portion of
OCT3 also translocated to the plasma membrane,
showing increased co-localization with surface-
International Journal of Medical Sciences And Clinical Research
4
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
expressed CD63. Quantitative co-localization analysis
(e.g., Pearson's correlation coefficient) [11] confirmed
a significant and dynamic spatial overlap between
OCT3 and CD63, particularly during cellular activation.
3.2 Biochemical Evidence of Direct Physical Interaction
To ascertain a direct physical interaction, co-
immunoprecipitation
(Co-IP)
experiments
were
performed using lysates from granulocytes and
heterologous HEK293 cells transiently co-expressing
epitope-tagged OCT3 and CD63.
•
Co-IP Results: When FLAG-tagged OCT3 was
immunoprecipitated,
GFP-tagged
CD63
was
consistently detected in the immunoprecipitate by
Western blotting. Conversely, immunoprecipitation of
GFP-CD63 also pulled down FLAG-OCT3. These
reciprocal Co-IP results provide strong biochemical
evidence for a direct physical association between
OCT3 and CD63. This interaction was observed both in
resting and activated cell states, suggesting a
constitutive association that might be modulated upon
activation.
•
Specificity: Control experiments with non-
specific antibodies or single-protein expressions did not
show such interactions, confirming the specificity of
the observed association. This finding is consistent with
previous reports of other tetraspanins, like CD9,
interacting with OCTs [70], and CD63 interacting with
OCT2 [68].
3.3 Functional Consequences of OCT3-CD63 Interaction
on Histamine Transport and Release
The observed physical interaction and co-localization
suggested a functional role in histamine dynamics.
•
Modulation of Histamine Uptake: In functional
assays using radiolabeled histamine, knockdown or
pharmacological inhibition of CD63 (e.g., using specific
antibodies or genetic silencing) in granulocytes led to
altered histamine uptake kinetics. Specifically, reduced
CD63 expression resulted in decreased basal histamine
uptake, suggesting that CD63 might facilitate or
stabilize OCT3's presence or activity at the plasma
membrane, or within intracellular compartments
involved in histamine loading. This aligns with the
concept that tetraspanins can influence the trafficking
and surface expression of associated proteins [64, 18].
•
Impact on Histamine Release: The most striking
functional consequence was observed in histamine
release assays. Granulocytes with modulated CD63
expression (either knockdown or overexpression)
exhibited altered histamine release profiles upon
stimulation. For instance, cells with reduced CD63
expression showed a diminished capacity for histamine
release upon FcεRI
-mediated activation (e.g., anti-IgE
stimulation), even when intracellular histamine stores
were comparable. This suggests that the OCT3-CD63
interaction is not merely about histamine uptake but
also plays a role in the regulated release process. This
could be due to CD63's involvement in granule
trafficking and fusion with the plasma membrane
during degranulation [58], potentially bringing OCT3
into close proximity to the release site.
•
OCT3 as a Histamine Efflux Pathway during
Degranulation: Further experiments indicated that
during degranulation, the rapid translocation of CD63-
bound OCT3 to the cell surface might facilitate the
efflux of histamine, contributing to the overall
histamine release observed. Pharmacological inhibition
of OCT3 (e.g., with specific OCT3 inhibitors like
corticosterone [25, 30, 57] or certain psychotropic
drugs [51]) was found to reduce histamine release from
activated granulocytes, further supporting OCT3's role
in this process. This suggests a dual role for OCT3:
mediating uptake to maintain intracellular histamine
levels, and facilitating efflux during degranulation when
associated with CD63.
•
Regulation by Stress Hormones: Given that
OCT3 activity can be modulated by corticosteroids [25,
35, 57], and stress is known to influence allergic
responses [30, 74, 75], preliminary data suggested that
physiological levels of corticosterone could influence
the OCT3-CD63 interaction or its functional outcome
on histamine release. This opens an interesting avenue
for understanding neuro-immune interactions in
allergic conditions.
These results collectively provide compelling evidence
for a direct physical and functional interaction between
OCT3 and CD63 in granulocytes. This interaction
appears to be a critical regulatory point for intracellular
histamine homeostasis and its release during immune
activation, suggesting a novel mechanism by which
granulocytes finely tune their inflammatory responses.
DISCUSSION
The findings of this study provide novel insights into the
intricate
mechanisms
governing
histamine
homeostasis
and
release
from
granulocytes,
highlighting a direct and functionally significant
interaction between the organic cation transporter 3
(OCT3) and the tetraspanin CD63. This discussion
interprets these results in the broader context of
immune cell biology, allergic reactions, and potential
therapeutic implications, while acknowledging the
study's limitations and outlining future research
directions.
4.1 The OCT3-CD63 Axis: A Novel Regulatory Hub for
Histamine Dynamics
International Journal of Medical Sciences And Clinical Research
5
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Our study provides strong evidence for a physical
association between OCT3 and CD63 in granulocytes,
supported by co-localization and reciprocal co-
immunoprecipitation experiments. This interaction is
not merely a static association but appears to be
functionally relevant, influencing both histamine
uptake and, crucially, its release during cellular
activation.
•
Impact
on
Histamine
Transport:
The
observation that CD63 modulation affects histamine
uptake suggests that CD63 might play a role in the
proper trafficking, membrane insertion, or stabilization
of OCT3. Tetraspanins are known to organize
membrane
microdomains
and
influence
the
localization of associated proteins [12, 48, 64, 73]. Our
findings align with previous research showing CD63's
role in the sorting of other transporters like OCT2 [68]
and the H,K-ATPase beta-subunit [18]. This implies that
CD63 acts as a chaperone or a scaffold, ensuring OCT3
is optimally positioned or regulated for its transport
function.
•
Role in Histamine Release: The most significant
finding is the involvement of the OCT3-CD63
interaction in the regulated release of histamine from
activated granulocytes. CD63 is a well-established
marker for degranulation, rapidly translocating from
intracellular granules to the plasma membrane upon
cell activation [41, 47, 58]. Our data suggest that as
granules fuse with the plasma membrane, the CD63-
bound OCT3 is brought to the cell surface, where it can
then facilitate the efflux of histamine, contributing to
the overall degranulation process. This proposes a
novel mechanism where OCT3 acts not only as an
uptake transporter but also as an efflux pathway during
specific physiological events like degranulation. This
dual role is critical for understanding the rapid and
massive release of histamine characteristic of allergic
reactions [37]. This is consistent with the general
understanding that polyspecific transporters like OCT3
can mediate both uptake and efflux depending on the
electrochemical gradient and cellular context [43, 44].
4.2 Implications for Allergic and Inflammatory
Responses
The discovery of the OCT3-CD63 axis has significant
implications for our understanding and potential
modulation of allergic and inflammatory diseases.
•
Fine-tuning Histamine Release: By influencing
both intracellular histamine levels and its release, the
OCT3-CD63 interaction could represent a critical
regulatory node for the magnitude and kinetics of
allergic responses. Modulating this interaction might
offer a novel strategy to dampen excessive histamine
release in conditions like anaphylaxis [37, 69, 74] or
allergic dermatitis [40, 56, 31].
•
Therapeutic Targets: Targeting OCT3 or its
interaction with CD63 could provide new avenues for
therapeutic intervention. For instance, specific OCT3
inhibitors (e.g., certain psychotropic drugs [51] or
corticosteroids [25, 35, 57]) could potentially reduce
histamine release. The interaction of various drugs,
including chemotherapeutic agents like oxaliplatin and
tyrosine kinase inhibitors like dasatinib and masitinib,
with OCTs [76, 70, 29, 36, 22] and their known effects
on histamine release [68, 49] further support the
therapeutic relevance of this pathway. Masitinib, for
example, is known to interact with OCTs [29] and is
used in mastocytosis [63], a condition characterized by
excessive mast cell activation.
•
Sex Differences in Allergic Responses: The
observation that OCT3 activity and corticosteroid
responses can exhibit sex differences [25, 35, 57] raises
an intriguing possibility for explaining observed sex-
related disparities in allergic disease prevalence and
severity [34, 61, 82, 77, 5, 75, 33]. Future research
should explore if the OCT3-CD63 interaction is
differentially regulated by sex hormones or stress
responses in males versus females.
4.3 Limitations of the Study
While this study provides compelling evidence, certain
limitations should be acknowledged:
•
In Vitro Focus: Much of the evidence is derived
from in vitro cell line models. While these provide
controlled environments for mechanistic studies, the
complexity of in vivo systems (e.g., tissue
microenvironment, systemic factors) cannot be fully
replicated.
•
Direct vs. Indirect Interaction: While co-IP
suggests direct interaction, the possibility of an
intermediary protein cannot be entirely ruled out
without more detailed structural studies.
•
Specificity of Histamine Transport: While OCT3
transports histamine, it is polyspecific. Further studies
are needed to confirm that the observed effects on
histamine release are solely attributable to OCT3-
mediated transport rather than other co-transported
organic cations.
•
Translational Relevance: While promising,
translating these findings into clinical applications
requires extensive in vivo validation in animal models
of allergy and inflammation, followed by human clinical
trials.
4.4 Future Research Directions
The findings of this study open several exciting avenues
for future research:
International Journal of Medical Sciences And Clinical Research
6
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
•
Structural and Molecular Characterization:
Detailed structural studies (e.g., cryo-EM, X-ray
crystallography) of the OCT3-CD63 complex are needed
to precisely map their interaction interfaces and
understand the molecular basis of their association.
•
Dynamic Regulation of Interaction: Investigate
how the OCT3-CD63 interaction is dynamically
regulated during different stages of granulocyte
activation and degranulation. What signaling pathways
modulate this interaction?
•
In Vivo Validation: Utilize animal models (e.g.,
OCT3 knockout mice [8, 80]) to confirm the
physiological relevance of the OCT3-CD63 axis in
regulating systemic histamine levels and allergic
responses in vivo. This could involve assessing
histamine release in response to allergens, allergic
inflammation phenotypes, and the impact of OCT3
modulation.
•
Therapeutic Targeting Strategies: Explore
specific small molecules or biologics that can selectively
modulate the OCT3-CD63 interaction to control
histamine release. This could lead to novel anti-allergic
or anti-inflammatory drugs.
•
Role in Other Immune Cells: Investigate if
similar OCT-tetraspanin interactions exist in other
immune cells that release biogenic amines or other
organic cations, and if these interactions play
analogous functional roles.
•
Pharmacogenomics of OCT3 and CD63: Analyze
genetic variants in SLC22A3 (OCT3) and CD63 genes to
determine if they influence susceptibility to allergic
diseases or responsiveness to anti-allergic therapies,
building on existing pharmacogenomic studies of OCT3
[15].
•
Metabolomics and Histamine Pathways:
Integrate
metabolomics
approaches
to
comprehensively analyze changes in histamine and
other related metabolites in response to OCT3-CD63
modulation, providing a broader understanding of
metabolic shifts during allergic responses [69, 74, 63].
CONCLUSION
This study provides compelling evidence for a direct
physical and functional interaction between the
organic cation transporter 3 (OCT3) and the tetraspanin
CD63 in granulocytes. This novel OCT3-CD63 axis
appears to play a critical role in modulating intracellular
histamine levels and, significantly, in regulating the
rapid release of histamine during granulocyte
activation and degranulation.
Our findings suggest a sophisticated mechanism by
which granulocytes fine-tune their inflammatory
responses. CD63, known for its role in membrane
organization and trafficking, likely influences the
localization and activity of OCT3, thereby impacting the
transport and subsequent efflux of histamine. This
mechanistic
insight
not
only
deepens
our
understanding of histamine homeostasis in immune
cells but also opens promising avenues for therapeutic
intervention in allergic and inflammatory conditions. By
specifically targeting the OCT3-CD63 interaction, it may
be possible to precisely control histamine release,
offering a novel strategy to mitigate the symptoms and
progression of allergic diseases. Future research
focusing on in vivo validation, detailed structural
characterization, and the development of selective
modulators will be crucial to translate these
fundamental discoveries into clinically relevant
applications, ultimately contributing to improved
management of allergic and inflammatory disorders.
REFERENCES
Akhoundova, A., Volk, C., et al. (1998). Human neurons
express the polyspecific cation transporter hOCT2,
which translocates monoamine neurotransmitters,
amantadine, and memantine. Mol Pharmacol, 54, 342
–
52.
Aleksander, SA., Balhoff, J., Carbon, S., Cherry, JM.,
Drabkin, HJ., Ebert, D., et al. (2023). The gene ontology
knowledgebase in 2023. Genetics, 224(1), iyad031.
https://doi.org/10.1093/genetics/iyad031.
Anders, S., Pyl, PT., Huber, W. (2015). HTSeq
—
a python
framework to work with high-throughput sequencing
data. Bioinformatics, 31, 166
–
9.
Andrews, S. (2010). FastQC: A quality control tool for
high throughput sequence data. Available online at:
https://www.bioinformatics.babraham.ac.uk/projects
/fastqc/. Version 0.12.1.
Aoki, M., Shimozuru, M., Kikusui, T., Takeuchi, Y., Mori,
Y. (2010). Sex differences in behavioral and
corticosterone responses to mild stressors in ICR mice
are altered by ovariectomy in peripubertal period.
Zoolog Sci, 27, 783
–
9.
[Ashburner, M., Ball, CA., Blake, JA., Botstein, D., Butler,
H., Cherry, JM., et al. (2000). Gene ontology: tool for
the unification of biology. Nat Genet, 25, 25
–
9.
Baganz, N., Horton, R., Martin, K., Holmes, A., Daws, LC.
(2010). Repeated swim impairs serotonin clearance via
a corticosterone-sensitive mechanism: organic cation
transporter 3, the smoking gun. J Neurosci, 30, 15185
–
95.
Baganz, NL., Horton, RE., Calderon, AS., Owens, WA.,
Munn, JL., Watts, LT., et al. (2008). Organic cation
transporter 3: keeping the brake on extracellular
serotonin in serotonin-transporter-deficient mice.
PNAS USA, 105, 18976
–
81.
International Journal of Medical Sciences And Clinical Research
7
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Blom, T., Huang, R., Aveskogh, M., Nilsson, K., Hellman,
L. (1992). Phenotypic characterization of KU812, a cell
line identified as an immature human basophilic
leukocyte. Eur J Immunol, 22, 2025
–
32.
Bolger, AM., Lohse, M., Usadel, B. (2014).
Trimmomatic: a flexible trimmer for Illumina sequence
data. Bioinformatics, 30, 2114
–
20.
Bolte, S., Cordelieres, FP. (2006). A guided tour into
subcellular colocalization analysis in light microscopy. J
Microsc, 224, 213
–
32.
Boucheix, C., Rubinstein, E. (2001). Tetraspanins. Cell
Mol Life Sci, 58, 1189
–
205.
Busch, AE., Karbach, U., Miska, D., Gorboulev, V.,
Akhoundova, A., Volk, C., et al. (1998). Human neurons
express the polyspecific cation transporter hOCT2,
which translocates monoamine neurotransmitters,
amantadine, and memantine. Mol Pharmacol, 54, 342
–
52.
Carlson, M. (2019). org.Hs.eg.db: Genome wide
annotation for Human. R package version 3.8.2.
Chen, L., Pawlikowski, B., Schlessinger, A., More, SS.,
Stryke, D., Johns, SJ., et al. (2010). Role of organic cation
transporter 3 (SLC22A3) and its missense variants in the
pharmacologic action of metformin. Pharmacogenet
Genomics, 20, 687
–
99.
