AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 1 79-G86, Copyright © 1985 by American Physiological Society
Mediation of muscarinic stimulation of pepsinogen secretion in the frog
M. Inoue, J. Fong, G. Shah and B. I. Hirschowitz
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.
