title: Mediation of muscarinic stimulation of pepsinogen secretion in the frog.
abstract: The in vitro release of pepsinogen secretion by the isolated esophagus of the American bullfrog was studied with an improved model system. The tissue was mounted in a double chamber that preserves mucosal polarity and provides both control and test segments, each 1 cm2 from the same tissue. Pepsinogen secretion was severalfold higher than previously found with mucosal strips and could be sustained for several hours. Bethanechol (BCh) caused concentration-dependent (0.1-50 microM) pepsinogen secretion with a Vmax of 74 +/- 12 micrograms X mg prot-1 X h-1 or 50-60% of total pepsinogen; Km was 3 microM and 500 microM BCh stimulated at less than the Vmax value. Atropine specifically blocked BCh and pA2 = 9.3. In the presence of 100 microM isobutylmethyxanthine, BCh produced a dose-dependent increase in tissue cAMP but not cGMP. BCh remained effective in Ca2+-free medium. In calcium-free medium EGTA concentration dependently (0.2-5 mM) suppressed the pepsinogen response to BCh. The evidence thus far suggests that cholinergic stimulation of pepsinogen secretion in the tissue acts via both cAMP and Ca2+. More specific studies would be required for absolute confirmation of either or both apparent mechanisms and to resolve how they interact.
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: J
authors.initials: J
authors.lastname: Fong
authors.forename: G
authors.initials: G
authors.lastname: Shah
authors.forename: B I
authors.initials: BI
authors.lastname: Hirschowitz
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D010435:Pepsinogens / Q000378:metabolism*; D011892:Rana catesbeiana; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
chemical_list: D001626:Bethanechol Compounds; D010435:Pepsinogens; D011976:Receptors, Muscarinic; D018723:Bethanechol; D004533:Egtazic Acid; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine