The involvement of calcium in the intestinal response to secretagogues in the rat.
The involvement of Ca2+ in the regulation of intestinal secretion was investigated in stripped sheets of rat mid-intestine. Removal of serosal Ca2+ together with the addition of EGTA at concentrations of 0.5 and 1 mM inhibited the rise in short-circuit current (s.c.c.) induced by both acetylcholine and theophylline, a similar degree of inhibition being observed with both secretagogues. Ca2+-free serosal fluid with 0.5 mM-EGTA added reduced significantly the rises in s.c.c. induced by A23187, acetylcholine, 5-hydroxytryptamine, theophylline, dibutyryl cyclic AMP and prostaglandin E2, but not the increased s.c.c. associated with glucose absorption. The Ca2+ channel blocker verapamil produced similar results. The calmodulin antagonist trifluoperazine inhibited secretagogue action while its sulphoxide derivative was without effect at the same concentration. The intracellular Ca2+ antagonist TMB-8 reduced the increased s.c.c. observed with acetylcholine and dibutyryl cyclic AMP. The net Cl- secretion, but not the decreased mucosal-to-serosal Na+ flux, induced by acetylcholine was abolished in Ca2+-free conditions. There was no consistent effect on the reduction in the residual ion flux caused by acetylcholine. Absence of Ca2+ converted the stimulation of Cl- secretion induced by dibutyryl cyclic AMP observed under control conditions to an enhancement of net Na+ and Cl- absorption. It is concluded that intestinal secretagogues, whether they act through cyclic AMP or not, require both internal and external sources of Ca2+ if they are to produce their full effects. Moreover, it appears that the nature of the response to dibutyryl cyclic AMP depends on the prevailing Ca2+ concentration.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D015232:Dinoprostone; D004533:Egtazic Acid / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007419:Intestinal Secretions / Q000187:drug effects*; D007422:Intestines / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002712:Chlorides; D011458:Prostaglandins E; D014268:Trifluoperazine; D012701:Serotonin; D000001:Calcimycin; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D003994:Bucladesine; D012964:Sodium; D013806:Theophylline; D014700:Verapamil; D015232:Dinoprostone; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium