Roles of σ Receptors in Isolated Guinea Pig Parietal Cells

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σ receptor involvement in the oxyntic mechanism of gastric parietal cells was investigated using isolated guinea pig parietal cells. Using the ^<14>C-aminopyrine accumulation method, di(orthotolyl)guanidine (DTG), a σ receptor agonist, demonstrated peak stimulation of acid production at a concentration of 5×10^<-5>M. The DTG-induced stimulatory effect on ^<14>C-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 σ receptor subtypes, σ 1 and σ 2, on the crude membranes of parietal cells. There was a direct relationship between DTG dose and intracellular Ca^<2+> 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 σ receptors exist on guinea pig gastric parietal cells and suggest that they play a role in acid production via an increase in intracellular Ca^<2+> concentration.
東海大学の論文