AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 4 622-G629, Copyright © 1988 by American Physiological Society
Stimulation of acid secretion and phosphoinositol production by rat parietal cell muscarinic M2 receptors
A. Pfeiffer, H. Rochlitz, A. Herz and G. Paumgartner
Medizinische Klinik II, Klinikum Grosshadern, University of Munich, West Germany.
The muscarinic receptor system involved in hydrogen ion production by
enriched rat gastric parietal cells was investigated. Muscarinic receptor
density determined by [N-methyl-3H]scopolamine binding was 8,100/cell. The
receptor appeared to be of the M2 muscarinic receptor subtype, since it had
a low affinity (Kd, 189 nM) for the M1 receptor antagonist pirenzepine
compared with atropine (Kd, 0.74 nM). Receptor activation by carbachol
rapidly augmented levels of polyphosphoinositides, indicating an activation
of a phospholipase C. The dose-response relations for the increase in
inositol phosphates closely paralleled the binding of carbachol to
muscarinic receptors with a Km of 17 microM. The inositol phosphate
response was antagonized by pirenzepine with a Ki of 177 nM. The
stimulation of inositol phosphate levels by carbachol correlated well with
the stimulation of [14C]aminopyrine uptake, determined as an index of acid
secretion. The muscarinic agonists oxotremorine, pilocarpine, and
bethanechol elicited partial increases in inositol phosphates at maximal
drug concentrations, and these partial increases correlated with their
ability to stimulate [14C]aminopyrine uptake. These data indicate that
inositol polyphosphates may be a second messenger of M2 receptors
stimulating acid secretion.
