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Journal of Neuroscience, Vol 9, 4150-4157, Copyright © 1989 by Society for Neuroscience
Cross-communication between acetylcholine and VIP in controlling catecholamine secretion by affecting cAMP, inositol triphosphate, protein kinase C, and calcium in rat adrenal medulla
RK Malhotra, TD Wakade and AR Wakade
Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan 48201.
The purpose of the present study was to determine the molecular mechanism
of stimulatory actions of ACh and vasoactive intestinal polypeptide (VIP)
by determining the role of various second messengers in the neurohumoral
secretion. Toward such a goal, we measured cAMP, cGMP, protein kinase (PKC)
activity, 3H-inositol triphosphate (3H-IP3), and 45Ca uptake in the adrenal
medulla subjected to various treatments. Stimulation of splanchnic nerve
endings increased 45Ca uptake, cAMP content, 3H-IP3, and PKC activity in
the adrenal medulla. If muscarinic receptors of chromaffin cells were
selectively activated by perfusion with muscarine, 3H-IP3 content and PKC
activity were enhanced. Nicotine, on the other hand, increased only 45Ca
uptake without affecting any other second messenger. Perfusion with VIP
increased PKC activity and cAMP and 3H-IP3 content. None of the procedures
affected cGMP content. Interplay among various second messengers was
further investigated by studying interactions of nicotinic, muscarinic, and
VIP- ergic receptors in modulation of catecholamine (CA) secretion and by
using agents known to activate specific second messengers (e.g., forskolin,
phorbol esters). Our results show that muscarine, VIP, and phorbol ester
facilitated nicotine-evoked secretion by increasing PKC activity, and it
was associated with an additional increase in 45Ca accumulation. On the
other hand, secretion evoked by nicotine as well as muscarine was
facilitated by forskolin without additional increase in 45Ca accumulation.
A novel feature of the study is that ACh and VIP activate three types of
receptors on chromaffin cells to stimulate and mutually facilitate the
secretion of CA by generating various second messengers.(ABSTRACT TRUNCATED
AT 250 WORDS)
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