Mediation of muscarinic stimulation of pepsinogen secretion in the frog.
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.
Inoue
M
M
Fong
J
J
Shah
G
G
Hirschowitz
B I
BI
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*
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