Organic cation transporter 1 participates in the immune response of <i>Pinctada fucata martensii</i> by regulating nAChR

Pinctada fucata martensii is an economically important mollusk in aquaculture, known for marine pearl production. The inflammatory response during the transplantation process was a key factor affecting pearl yield. Our previous studies have revealed the critical role of nicotinic acetylcholine receptors (nAChRs) from P. f. martensii in transplantation immunity. In this study, we obtained the 2,000 bp upstream sequence of the PmnAChR-6 gene and constructed promoter truncation plasmids, demonstrating that the core promoter activity region is located within the 1 to 500 bp upstream of the coding sequence. Organic cation transporter 1 (OCT-1) was predicted to be a key regulatory factor in the promoter region of PmnAChR-6. The dual luciferase assay results indicate that overexpression of OCT-1 reduces the promoter activity of the PmnAChR-6. Transcriptomic analysis of the pearl oyster after OCT-1 inhibitor (benzoylpaeoniflorin) treatment revealed that downregulation of PmOCT-1 led to significant enrichment of pathways such as apoptosis and endocytosis, along with elevated interleukin-17 levels in the serum. Furthermore, OCT-1 inhibitor treatment improved both the survival and nucleus retention rates of the transplanted pearl oysters. These findings indicate that PmOCT-1 participates in immune response by regulating expression of PmnAChR-6. The results of this study provide potential targets for effectively modulating immune responses during pearl production.