Pacap stimulates catecholamine release from the adrenal medulla in
vivo in rats: a possible novel non-cholinergic secretagogue.
Watanabe, Takuya, Norio Shimamoto, Akiko Takahashi, and Masahiko
Fujino.
Discovery Research Laboratories I, Discovery Research Division,
Molecular Pharmacology Laboratory, Pharmaceutical Research Division,
Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki,
Japan
APStracts 2:0147E, 1995.
The secretory response of the adrenal medulla to pituitary adenylate
cyclase activating polypeptide (PACAP), a novel polypeptide with 68%
structural homology to vasoactive intestinal polypeptide (VIP), was
investigated in anesthetized rats using in vivo microdialysis. The
injection of PACAP (1.5 nmol) caused a greater amount of increase in
catecholamine concentration than carbachol (30 nmol) or VIP (30 nmol)
in the dialysate for a period of 60 min. The ratios of noradrenaline
to adrenaline in the dialysate after stimulation with these compounds
did not differ from resting conditions. The simultaneous application
of both nicotinic and muscarinic antagonists (10 mM mecamylamine and
1 mM atropine) eliminated the increase in catecholamine secretion
induced by carbachol. In contrast, PACAP-induced secretion of
catecholamine was not inhibited by these cholinergic antagonists.
These data led to the following conclusions: 1) PACAP was more potent
than either carbachol or VIP in enhancing the secretion of
catecholamine from the adrenal medulla and 2) PACAP-induced
catecholamine secretion was due to the direct action of PACAP on the
adrenal medulla, rather than an indirect action mediated by
acetylcholine release. These results strongly suggest that PACAP is a
non-cholinergic secretagogue of the adrenal medulla in rats.
Received 19 December 1994; accepted in final form 22 June 1995.
APS Manuscript Number E525-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.