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.

Organic Cation Transporter 3, Histamine Release, Granulocytes

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