The role of store-operated Ca 2+ channels in adrenocorticotropin release by rat pituitary cells

Abstract

In this study, we investigated the role of store-operated Ca 2+ channels (SOCC) on ACTH release using microperifusion system. The SOCC blockers, SKF96365 and MRS1845, did not affect the ACTH response to single AVP stimulation. After the depletion of intracellular Ca 2+ stores by treating with ionomycin, SOCC blockers reduced the initial spike phase of ACTH response to AVP, which is mediated by inositol 1,4,5-trisphosphate-induced intracellular Ca 2+ release from the endoplasmic reticulum (ER). The sustained plateau phase of ACTH response, which is mediated by protein kinase C leading Ca 2+ influx via L-type voltage-dependent Ca 2+ channels, was not affected. Addition of L-type voltage-dependent Ca 2+ channel blocker nimodipine with the SOCC blockers reduced both the initial spike and sustained phases of ACTH response to AVP. Even after ER Ca 2+ depletion, the SOCC blockers did not affect the ACTH response to CRH, which is mediated by cAMP-dependent protein kinase A. Transient receptor potential (TRP) C channel is the strongest candidate for SOCC, and RT-PCR revealed that all types of TRPC homologue mRNA were expressed in rat anterior pituitary cells. In conclusion, the SOCC mediates the initial spike phase of ACTH response to AVP, possibly via ER Ca 2+ store refilling to induce maximum response.