Enhanced calcium signaling and acid secretion in parietal cells isolated from gastrin-deficient mice.
Gastrin-deficient mice have impaired basal and agonist-stimulated gastric acid secretion. To analyze whether an intrinsic parietal cell defect contributed to the reduced acid secretion, we analyzed parietal cell calcium responses and acid secretory function in vitro. Parietal cells were purified by light-scatter cell sorting and calcium responses to gastrin, histamine, and carbachol were measured in gastrin-deficient and wild-type mice cell preparations. Surprisingly, basal and histamine-induced calcium concentrations were higher in the mutant cell preparations. [(14)C]aminopyrine uptake analysis in acutely isolated gastric glands revealed that basal acid accumulation was enhanced in gastrin-deficient cell preparations as well as on treatment with carbachol or histamine. These results suggested that an intrinsic parietal cell defect was not responsible for the reduced acid secretion in gastrin-deficient mice. Flow cytometric analysis of dispersed, H(+)-K(+)-ATPase-immunostained gastric mucosal preparations revealed a marked increase in parietal cell number in gastrin-deficient mice, which may have accounted for the enhanced in vitro acid secretion detected in this study. Parietal cells were found to be significantly smaller in the mutant cell preparations, suggesting that gastrin stimulation modulates parietal cell morphology.
Hinkle
Karen L
KL
Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Bane
Gina C
GC
Jazayeri
Ali
A
Samuelson
Linda C
LC
D000632:Aminopyrine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002469:Cell Separation; D018679:Cholinergic Agonists / Q000494:pharmacology; D005434:Flow Cytometry; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000235:genetics* / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002250:Carbon Radioisotopes; D018679:Cholinergic Agonists; D005755:Gastrins; D000632:Aminopyrine; D006632:Histamine; D002217:Carbachol