Roles of sigma receptors in isolated guinea pig parietal cells.
Sigma receptor involvement in the oxyntic mechanism of gastric parietal cells was investigated using isolated guinea pig parietal cells. Using the 14C-aminopyrine accumulation method, di(orthotolyl)guanidine (DTG), a sigma receptor agonist, demonstrated peak stimulation of acid production at a concentration of 5 x 10(-5) M. The DTG-induced stimulatory effect on 14C-aminopyrine accumulation in preparations enriched in parietal cells was inhibited by haloperidol, a DTG inhibitor, and omeprazole, a proton pump inhibitor, in a concentration-dependent manner. Assessment of the interaction between DTG and agonists for histamine, gastrin, and muscarine receptors demonstrated a potentiating interaction effect on acid production only when parietal cells were exposed to both DTG and histamine. A receptor-binding assay using 3H-DTG revealed two sigma receptor subtypes, sigma 1 and sigma 2, on the crude membranes of parietal cells. There was a direct relationship between DTG dose and intracellular Ca2+ concentration, but there was no change in intracellular cyclic adenosine 5'-monophosphate (cAMP) concentration when parietal cells were exposed to DTG. These results demonstrate that sigma receptors exist on guinea pig gastric parietal cells and suggest that they play a role in acid production via an increase in intracellular Ca2+ concentration.
Suzuki
T
T
6th Department of Internal Medicine, School of Medicine, Tokai University, Kanagawa, Japan.
Tani
N
N
Mutoh
N
N
Miwa
T
T
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D007553:Isotope Labeling; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D014316:Tritium
D002250:Carbon Radioisotopes; D006146:Guanidines; D017480:Receptors, sigma; D000632:Aminopyrine; D014316:Tritium; D000242:Cyclic AMP; C050232:1,3-ditolylguanidine; D002118:Calcium