Calcitriol attenuates the basal and vasoactive intestinal peptide-stimulated cAMP production in prolactin-secreting rat pituitary (GH4C1) cells

Abstract A clonal strain of prolactin-producing rat pituitary tumour cells (GH 4 C 1 cells) was used to study the effect of calcitriol on cyclic adenosine monophosphate (cAMP) production. Calcitriol (10 nM) attenuated both the basal and vasoactive intestinal peptide (VlP)-stimulated cAMP production after 2 days' pretreatment of the cells. The effect was detectable at 1 nM and maximal at about 10 nM. Calcitriol was at least 100 times more potent than calcidiol and 24-hydroxycalcidiol. Calcitriol (10 nM, 4 days) did not affect the specific binding of 125 I-VIP, but attenuated the guanosine 5′- O -(3-thiotriphosphate) (GTP-γS)-stimulated (100 μM) adenylyl cyclase activity by 25%. Calcitriol (10 nM, 4 days) also attenuated both the Mn 2+ (1 mM) and the forskolin-stimulated (10 /gmM) adenylyl cyclase activity by 43 and 41%, respectively. In conclusion, these data suggest that calcitriol attenuates the basal and VIP-stimulated cAMP production by inhibiting the catalytic subunit of the adenylyl cyclase as well as the amount of the G protein G s α.