Cholecystokinin, carbachol, gastrin, histamine, and forskolin increase [Ca2+]i in gastric glands.
The Ca2+-selective fluorescent probe quin 2 was used to measure changes in the concentration of free cytosolic [Ca2+] in isolated rabbit gastric glands. Both carbachol and cholecystokinin octapeptide (CCK-8) were found to increase transiently intracellular Ca2+ concentration, [( Ca2+]i) with maximal increases from approximately 0.15 to 0.5 microM occurring within 4-6 s following secretagogue addition. Increases in [Ca2+]i were dose dependent and inhibited by appropriate antagonists. Prestimulation with either carbachol or CCK-8 effectively prevented increases in [Ca2+]i in response to the other agonist. Acute removal of extracellular Ca2+ slightly reduced the increase in [Ca2+]i that occurred following secretagogue addition but had no effect on pepsinogen secretion. Severe Ca2+ depletion resulted in potent inhibition of the quin 2 signal and suppressed basal pepsinogen release and reduced, but did not totally block, pepsinogen release in response to carbachol and CCK-8. Gastrin stimulation also elevated [Ca2+]i in glands, but this agonist was only 40-50% as effective as CCK-8. The cAMP-dependent agonists histamine and forskolin increased [Ca2+]i to approximately the same degree as gastrin. There was a definite lag in the rise in [Ca2+]i following simulation with histamine and forskolin compared with carbachol and CCK-8, which suggests that additional biochemical events occur between agonist-receptor binding and the rise in [Ca2+]i observed with the cAMP-dependent agonists. Both cAMP-dependent and -independent agonists induced an increase in autofluorescence that was slower than the rise in [Ca2+]i but equally affected by extracellular Ca2+ depletion.
D000634:Aminoquinolines; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005456:Fluorescent Dyes; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010435:Pepsinogens / Q000378:metabolism; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D000634:Aminoquinolines; D005456:Fluorescent Dyes; D005755:Gastrins; D010435:Pepsinogens; D005576:Colforsin; D003995:Dibutyryl Cyclic GMP; D001285:Atropine; D006632:Histamine; D002217:Carbachol; D012844:Sincalide; C035739:Quin2; D002118:Calcium