Regulation of [Ca2+]i by secretagogue stimulation of canine gastric parietal cells.
The ability of gastrin, histamine, and carbachol to stimulate acid secretion by direct action on gastric parietal cells is well established but the role of intracellular Ca2+ concentration ([Ca2+]i) in mediating these effects is the subject of some controversy. To examine this issue further, secretagogue-mediated changes in [Ca2+]i in single isolated canine gastric parietal cells were examined by microspectrofluorometry of fura-2-loaded cells. Resting [Ca2+]i in single parietal cells was 63 +/- 6 (SE) nM. Carbachol, 10(-5) M, induced a maximum elevation in [Ca2+]i with an initial transient rise of 178 +/- 24 (SE) nM, which was maintained in the absence of extracellular Ca2+ and a sustained plateau of 112 +/- 20 (SE) nM, which was abolished by removal of extracellular Ca2+. Both effects were reversed by the muscarinic receptor antagonist atropine. Gastrin (10(-9)-10(-7) M) also induced a bimodal rise in [Ca2+]i with a maximal initial transient rise of 206 +/- 14 nM and a sustained plateau of 94 +/- 9 nM. Both components of the [Ca2+]i response to gastrin were reversed by the gastrin specific antagonist L 365260. Lower concentrations of gastrin (10(-10) M) induced repetitive transient increases (oscillations) in cytosolic Ca2+. The amplitude of the first spike was less than 50% of the transient rise in [Ca2+]i stimulated by 10(-8) M gastrin. The oscillations occurred at a rate of 0.9/min, gradually decreasing in amplitude within 15 min of secretagogue administration. Histamine (10(-4) M) led to a minimal rise in [Ca2+]i (less than 5% of control) in less than 10% of the canine parietal cells tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Delvalle
J
J
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Tsunoda
Y
Y
Williams
J A
JA
Yamada
T
T
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism*; D010671:Phenylurea Compounds; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013050:Spectrometry, Fluorescence
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; C058121:L 365260; C013550:gastrin 17; D006632:Histamine; D002217:Carbachol; D002118:Calcium