Abstract: | Vasoactive intestinal peptide (VIP) has been shown to be steroidogenic in monolayer cultures of a murine adrenal tumor but must be present at concentrations about 100-fold greater than ACTH to elicit the same degree of stimulation. Both peptides enhanced cAMP synthesis, although there was again a difference of 2 orders of magnitude in the dose-response curves. In contrast, VIP stimulated adenyl cyclase activity of tumor membranes in the same concentration range as ACTH. Maximum activity with VIP was less than that with ACTH in the absence or presence of a saturating amount of guanylyl imido-diphosphate. Saturating amounts of both peptides stimulated activity to levels greater than that with either ACTH or VIP alone, but the activity was not fully additive. An o-nitrophenyl sulfenyl derivative of ACTH inhibited ACTH-stimulated adenyl cyclase activity but not VIP-stimulated activity. Low concentrations of calcium potentiated the ability of submaximal doses of ACTH to stimulate adenyl cyclase but had no effect on the response to VIP. Concentrations of secretin or glucagon comparable to that of VIP did not stimulate steroidogenesis in intact cells. These data suggest that VIP may bind to a unique receptor which may be distinct from that of ACTH. |