Acid secretagogues induce Ca2+ mobilization coupled to K+ conductance activation in rat parietal cells in tissue culture.
Intracellular recordings from cultured parietal cells of the rat gastric fundus showed that carbachol, pentagastrin, histamine (in the presence of isobutylmethylxanthine; IBMX) and dibutyryl cyclic AMP induced hyperpolarizing responses which were sensitive to a K+ channel blocker, quinine. The Ca2+ ionophore, ionomycin, also induced a quinine-sensitive hyperpolarization. Deprivation of extracellular Ca2+ preferentially inhibited the hyperpolarizing responses to histamine (plus IBMX) and to dibutyryl cyclic AMP. Caffeine, oxalate and dantrolene sodium, which are known to affect Ca2+ transport in the endoplasmic reticulum, selectively inhibited the carbachol response. Mitochondrial inhibitors (KCN and carbonylcyanide p-trifluoromethoxyphenylhydrazone) preferentially suppressed the gastrin response. Cytosolic Ca2+ measurements with fura-2 indicated that significant increases in the intracellular concentration of free Ca2+ were induced not only by Ca2+-mediated acid secretagogues (carbachol and gastrin), but also by a cyclic AMP-mediated secretagogue (histamine plus IBMX). Dibutyryl cyclic AMP also increased cytosolic Ca2+ ions. It is concluded that stimulation of receptors to histamine, carbachol and gastrin gives rise to mobilization of Ca2+ ions into the cytoplasm from the different sources, thereby stimulating Ca2+-activated K+ channels in cultured rat parietal cells.
Department of Internal Medicine, Kyoto University Faculty of Medicine, Japan.
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Ueda
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Okada
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D046508:Culture Techniques; D003600:Cytosol / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects*; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010418:Pentagastrin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology; D051381:Rats
D015221:Potassium Channels; D002217:Carbachol; D011803:Quinine; D010418:Pentagastrin; D002118:Calcium