Muscarinic receptor enhancement of nicotine-induced catecholamine secretion may be mediated by phosphoinositide metabolism in bovine adrenal chromaffin cells.

E J Forsberg,E Rojas,H B Pollard

doi:10.1016/s0021-9258(19)89192-5

Abstract

Bovine adrenal chromaffin cells possess both nicotinic and muscarinic cholinergic receptors, but only nicotinic receptors have heretofore appeared to mediate Ca2+-dependent exocytosis. We have now found that muscarinic receptor stimulation in bovine adrenal chromaffin cells leads to enhanced inositol phospholipid metabolism as evidenced by the rapid (less than 1 min) formation of inositol trisphosphate (IP3) and inositol bisphosphate (IP2). Muscarinic receptor-mediated accumulation of IP3 and IP2 continues beyond 1 min in the presence of LiCl and is accompanied by large increases in inositol monophosphate. Muscarinic receptor stimulation was also found to enhance nicotine-induced catecholamine secretion by 1.7-fold if muscarine was added 30 s before nicotine addition. Moreover, since the muscarinic antagonist atropine reduces acetylcholine-induced secretion, we conclude that muscarinic receptor stimulation somehow primes these cells for nicotinic receptor-mediated secretion, perhaps by causing small nonstimulatory increases in cytosolic free Ca2+ mediated by IP3. Furthermore, we show that small depolarizations of these cells with 10 mM K+, which themselves do not affect basal secretion, also enhance nicotine-induced secretion. Thus, small increases in cytosolic free Ca2+ produced either by physiologic muscarinic receptor stimulation or by small experimental depolarizations with K+ may prime the chromaffin cells for nicotinic receptor-mediated secretion.

Highlights

Bovine adrenal chromaffin cells possess both nicotinic and muscarinic cholinergic receptors, but only nicotinic receptors have heretofore appeared to mediate Cas+-dependent exocytosis
Biphasic Inositol Phosphate Accumulation Induced by cholinergic Receptor Stimulation-The effects of carbachol on inositol phosphate levels were evaluated by fist incubating the chromaffincellswith my0-[2-~H]inositolto achievea steady state, which occurred between36 and 48 h
Bovine adrenal chromaffin cells have presented an experimental enigma to the generalization that phosphoinositide metabolism leads to an increase in cytosolic free Ca2+(12)

Summary

Introduction

Bovine adrenal chromaffin cells possess both nicotinic and muscarinic cholinergic receptors, but only nicotinic receptors have heretofore appeared to mediate Cas+-dependent exocytosis. No direct measurements of IPSaccumulation have been reported, recent evidence suggests that muscarinic receptor stimulation can cause.a small increase in cytosolicfreeCa2+ in bovine adrenal chromaffin cells [25, 52].

Results

Conclusion