Dissociation between oxyntic cell cAMP formation and HCl secretion in bullfrog gastric mucosa.

Abstract

With the isolated bullfrog [Rana catesbeiana] gastric mucosa, direct measurement of c[cyclic]AMP together with acid secretory measurements showed that under a variety of conditions steady-state mucosal cAMP concentrations are not correlated with the secretory response of this tissue. In time course experiments, although the phosphodiesterase inhibitor, theophylline, allowed large increases in cAMP levels as early as 1 min after addition, other secretagogues, including histamine, carbachol, and pentagastrin, did not detectably increase cAMP at any sampling time between 1 and 60 min after addition. Because the intact gastric mucosa is composed of at least 3 tissue compartments, i.e., surface cells (sc), oxyntic cells (oc), and stroma (s), further experiments were performed to estimate cAMP concentrations in the oxyntic cells alone. Carbacol (10-4 M), pentagastrin (10-5 M), and theophylline (5 mM) stimulated comparable increases in oxyntic cell respiration. The response to histamine was somewhat smaller. In these same tissues, theophylling caused large increases in oxyntic cell cAMP, but the other secretagogues did not detectably alter cAMP levels. In other experiments, the phosphodiesterase inhibitor, papaverine, did not stimulate acid secretion under conditions under which it stimulated large increases in mucosal cAMP concentrations. Simultaneous addition of histamine plus papaverine did stimulate a secretory response. There is a lack of quantitative correlation between both mucosal and oxyntic cell cAMP levels and acid secretion. The secretagogues, histamine, carbachol, and pentagastrin may act by some mechanism that does not include cAMP. Under appropriate conditions, however, cAMP may also stimulate secretion. These conclusions are based on measurements of total cellular cAMP concentrations,which have not been proven to accurately reflect changes in the physiologically active component.