Limited accumulation of cyclic AMP underlies a modest vasoactive-intestinal-peptide-mediated increase in cytosolic [Ca2+] transients in GH3 pituitary cells.

The 4-chlorophenylthio analogue of cyclic AMP evoked profound and long-lasting changes in cytosolic [Ca2+] ([Ca2+]i) in pituitary-derived GH3 cells. However, vasoactive intestinal peptide (VIP), a hormone considered to act via cyclic AMP, was ineffective in modulating [Ca2+]i. The ability of VIP to modulate [Ca2+]i was enhanced by treatments that increased intracellular cyclic AMP. Much greater concentrations of intracellular cyclic nucleotides were achieved by the analogue than with VIP, under any condition. Thus cyclic AMP may play a prominent role in regulating [Ca2+]i in these cells, but the ability of hormones to stimulate its synthesis is limited, leading to a weak action on [Ca2+]i.