title: Vasoactive intestinal peptide potentiates and directly stimulates catecholamine secretion from rat adrenal chromaffin cells.
abstract: The actions of vasoactive intestinal polypeptide (VIP) on catecholamine secretion and changes in [Ca2+]i in single rat chromaffin cells were studied using amperometry and Indo-1. Application of VIP prior to acetylcholine (ACh) or co-application of VIP and ACh enhanced secretion by 94% and 153% respectively, compared to ACh alone. [Ca2+]i was increased by 17% when VIP was preapplied and by 73% upon co-application. Exposure to VIP before stimulation with 60 mM K+ enhanced secretion by 68%, but not [Ca2+]i. VIP application prior to DMPP and nicotine had no effect on [Ca2+]i, but increased [Ca2+]i signals to muscarine by 18%. VIP co-application potentiated only [Ca2+]i responses to muscarine, by 28%. The effect of VIP on muscarine-induced [Ca2+]i signals was mimicked by 8-Br-cAMP, and both were blocked by H-89, a protein kinase A inhibitor. Long-lasting increases in secretion accompanied by a sustained rise in [Ca2+]i to VIP alone were seen in 55% of cells. Removal of Ca2+ or addition of La3+ inhibited both responses, while L-, N- and P-type Ca2+ channel blockers were ineffective. SK&F 96365 inhibited VIP-induced secretion completely and rises in [Ca2+]i by 75%. Neither 8-Br-cAMP nor 8-Br-cGMP evoked responses similar to VIP alone. Thus in rat chromaffin cells, VIP acts both directly as a neurotransmitter in provoking sustained catecholamine secretion in a cAMP-independent manner, and also by enhancing ACh-induced secretion, via a cAMP-dependent action involving muscarinic receptors.
authors.affiliation: Laboratoire de Pharmacologie et Physiopathologie Cellulaires-CNRS URA600, Université Louis Pasteur de Strasbourg, B.P. 24, F-67401 Illkirch, France.
authors.forename: M
authors.initials: M
authors.lastname: Anderova
authors.forename: A D
authors.initials: AD
authors.lastname: Duchêne
authors.forename: J G
authors.initials: JG
authors.lastname: Barbara
authors.forename: K
authors.initials: K
authors.lastname: Takeda
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D007093:Imidazoles / Q000494:pharmacology; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D002395:Catecholamines; D007093:Imidazoles; D018721:Muscarinic Agonists; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D009116:Muscarine; D020866:omega-Conotoxin GVIA; D000242:Cyclic AMP; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium