AJP - Gastrointestinal and Liver Physiology, Vol 258, Issue 6 982-G987, Copyright © 1990 by American Physiological Society
Functionally distinct muscarinic receptors on gastric somatostatin cells
M. L. Schubert and J. Hightower
Department of Medicine, Medical College of Virginia, Richmond.
The present study was designed to examine the mode of action of muscarinic
agonists on somatostatin secretion in intact gastric tissues, i.e., mucosal
segments from the fundus and antrum of rat and the isolated luminally
perfused mouse stomach. Methacholine caused similar decreases in
somatostatin secretion in segments from the fundus (35 +/- 3%; P less than
0.001) and antrum (35 +/- 2%; P less than 0.001) of rat stomach, and in
whole mouse stomach (43 +/- 3%; P less than 0.001). The decrease was the
net effect of a dominant inhibition and a lesser stimulation of
somatostatin secretion. Pretreatment with the permeant derivative of the
acetomethoxy ester form of the calcium chelator
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM, 15
microM) caused a further decrease in methacholine-induced somatostatin
secretion, implying that a stimulatory component existed that was mediated
by intracellular calcium. Pretreatment with pertussis toxin (125 ng/ml) for
60 min converted the decrease in somatostatin secretion to an increase
above basal levels. The increase induced by pretreatment with pertussis
toxin was abolished by additional pretreatment with BAPTA/AM. Procaine (5
mM), which blocks release of calcium from intracellular stores, produced an
effect on somatostatin secretion similar to that of BAPTA/AM. The results
indicate that 1) methacholine exerts dual inhibitory and stimulatory
effects on somatostatin cells of rat and mouse stomach, 2) the dominant
effect is inhibitory and sensitive to pertussis toxin, and 3) a concurrent
stimulatory effect, mediated by calcium, is unmasked after blockade of the
inhibitory effect with pertussis toxin.
