Role of L-type Ca2+ channel in PACAP-induced adrenal catecholamine release in vivo.
The aim of the present study was to investigate whether the dihydropyridine-sensitive L-type Ca2+ channel is operative in adrenal catecholamine (CA) secretion induced by a novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. All drugs tested were locally infused into the left adrenal gland via the left adrenolumbar artery. PACAP, with the isoform consisting of 27 (PACAP-27) and 38 (PACAP-38) amino acid residues, significantly increased CA output in a dose-dependent manner, with doses ranging from 5 to 500 ng and 7 to 700 ng, respectively. However, the amplitude of epinephrine response to PACAP-27 was three times greater than that obtained with PACAP-38 at the highest dose tested. In a separate group, a single dose of PACAP-27 (50 ng) induced highly reproducible CA responses when the same dose was repeated with an interval of 35 min. In dogs treated with nifedipine (50 microg), 5 min before the second administration of PACAP-27, the net CA response was significantly inhibited by approximately 50% compared with that obtained in the presence of vehicle. A similar CA response to BAY K 8644 (5 microg) was completely abolished by the same dose of nifedipine. The present results indicate that both PACAP-27 and PACAP-38 have the direct local secretagogue effect on the adrenal medulla in vivo and that CA responses to PACAP-27 were greater than those observed with PACAP-38 at equivalent mole doses. The study suggests that the dihydropyridine-sensitive L-type Ca2+ channel is functionally involved in PACAP-induced adrenal CA secretion in the canine adrenal medulla in vivo.
Geng
G
G
Group de Recherche sur le Système Nerveux Autonome, Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Gaspo
R
R
Trabelsi
F
F
Yamaguchi
N
N
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009543:Nifedipine; D009638:Norepinephrine; D004837:Epinephrine