VASOACTIVE-INTESTINAL-PEPTIDE POTENTIATES AND DIRECTLY STIMULATES CATECHOLAMINE SECRETION FROM RAT ADRENAL CHROMAFFIN CELLS

The actions of vasoactive intestinal polypeptide (VIP) on catecholamin e secretion and changes in [Ca2+](i) in single rat chromaffin cells we re studied using amperometry and Indo-1. Application of VIP prior to a cetylcholine (ACh) or co-application of VIP and ACh enhanced secretion by 94% and 153% respectively, compared to ACh alone. [Ca2+](i) was in creased by 17% when VIP was preapplied and by 73% upon co-application. Exposure to VIP before stimulation with 60 mM K+ enhanced secretion b y 68%, but not [Ca2+](i). VIP application prior to DMPP and nicotine h ad no effect on [Ca2+](i), but increased [Ca-2+](i) signals to muscari ne by 18%. VIP co-application potentiated only [Ca2+](i) responses to muscarine, by 28%. The effect of VIP on muscarine-induced [Ca2+](i) si gnals was mimicked by 8-Br-cAMP, and both were blocked by H-89, a prot ein kinase A inhibitor. Long-lasting increases in secretion accompanie d by a sustained rise in [Ca2+](i) to VIP alone were seen in 55% of ce lls. Removal of Ca2+ or addition of La3+ inhibited both responses, whi le L-, N- and P-type Ca2f channel blockers were ineffective. SK&F 9636 5 inhibited VIP-induced secretion completely and rises in [Ca2+](i) by 75%. Neither 8-Br-cAMP nor 8-Br-cAMP evoked responses similar to VIP alone. Thus in rat chromaffin cells, VIP acts both directly as a neuro transmitter in provoking sustained catecholamine secretion in a cAMP-i ndependent manner, and also by enhancing ACh-induced secretion, via a cAMP-dependent action involving muscarinic receptors. (C) 1998 Elsevie r Science B.V. All rights reserved.