Differential effects of extracellular calcium removal and nonspecific effects of Ca2+ antagonists on acid secretory activity in isolated gastric glands.
The role of extracellular calcium in the action of the secretagogues, carbachol, histamine and forskolin, on parietal cell HCl secretion was investigated using glands isolated from rabbit gastric mucosa. Omission of calcium from the cellular incubation medium and chelation of a major portion of contaminating calcium with EGTA resulted in a disappearance of the initial transient response to carbachol (as measured by uptake of the weak base, amino[14C]pyrine), but the sustained response to carbachol persisted. Neither histamine nor forskolin-stimulated increase in amino[14C]pyrine uptake were affected by omission of extracellular calcium. Furthermore, the potentiating interactions between histamine and carbachol and between forskolin and carbachol appeared to occur independent of extracellular calcium. Attempts to assess the contribution of intracellular calcium to secretory activity using the Ca2+ antagonists, verapamil, nifedipine, nicardipine and lanthanum, and the putative intracellular Ca2+ antogonist, TMB-8 (3,4,5-trimethyloxybenzoic acid 8-(diethyl-amino)-octyl ester) were unsuccessful. Nifedipine had no effect on secretagogue stimulated amino[14C]pyrine accumulation even at concentration well above the pA2 reported for excitable tissues. Verapamil, nicardipine, lanthanum and TMB-8 all appeared to have nonspecific inhibitory effects on amino [14C]pyrine uptake. From these results we conclude that: (1) parietal cell HCl secretion can occur independent of extracellular Ca2+; (2) influx of extracellular Ca2+ enhances the response to carbachol but has little influence on the secretory response initiated by cAMP-dependent secretagogues; and (3) parietal cell Ca2+ channels have a different molecular configuration than Ca2+ channels in excitable cells.
D000632:Aminopyrine; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D005576:Colforsin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005088:Exocrine Glands / Q000187:drug effects / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism*; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011817:Rabbits
D002250:Carbon Radioisotopes; D000632:Aminopyrine; D005576:Colforsin; D004533:Egtazic Acid; D006632:Histamine; D002217:Carbachol; D002118:Calcium