Ca2+-dependent and -independent secretagogue action on gastric mucus secretion in rabbit mucosal explants.
The secretion of high-molecular weight glycoprotein was studied in rabbit antral and fundic explants in response to acetylcholine (ACh), the calcium ionophore A23187, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), forskolin, histamine, pentagastrin, and prostaglandin E2 (PGE2). Glycoprotein secretion was measured in pulse-chase experiments by incorporation of [14C]N-acetyl-D-glucosamine into explants and quantification of the secreted high-molecular weight-labeled glycoprotein. All tested agents except histamine and pentagastrin stimulated glycoprotein secretion in a concentration-dependent manner. The response to A23187 was abolished by removal of extracellular Ca2+ and greatly reduced by the calmodulin antagonist N-(6-amino-hexyl)-l-naphthalenesulfonamide (W7). The response to ACh was abolished by equimolar concentrations of atropine and by depletion of intracellular Ca2+ stores, an effect which was reversible on addition of Ca2+, and reduced by W7. The response to forskolin and PGE2 was not significantly affected by either extracellular or intracellular Ca2+ depletion. The combination of ACh with forskolin and A23187 with TPA had a synergistic effect on secretion. The absolute dependence of cholinergic stimulation on the presence of intracellular Ca2+ and the Ca2+-independent stimulatory effect of forskolin and PGE2 suggest that gastric mucus secretion can be elicited by at least two distinct pathways.
Seidler
U
U
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, FRG.
Sewing
K F
KF
D000109:Acetylcholine / Q000494:pharmacology; D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005748:Gastric Fundus / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008970:Molecular Weight; D009924:Organ Culture Techniques; D010418:Pentagastrin / Q000494:pharmacology; D011706:Pyloric Antrum / Q000378:metabolism; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002147:Calmodulin; D006023:Glycoproteins; D013449:Sulfonamides; D005576:Colforsin; D000001:Calcimycin; C017967:W 7; D001285:Atropine; D006632:Histamine; D010418:Pentagastrin; D015232:Dinoprostone; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D000117:Acetylglucosamine