Effect of inhibitors and weak bases on electrophysiology and secretion in frog stomach.

Abstract

Studies on the in vitro frog gastric mucosa are contrary to previous reports because imidazole does not inhibit H+ secretion. With a Rana pipiens in vitro preparation, imidazole when added to the nutrient side markedly decreases the measured H+ rate, but this decrease results from neutralization of secreted H+ by the imidazole diffusing from the nutrient to the secretory side. Inhibition of H+ secretion by thiocyanate is substantially reversed by imidazole. Another weak base, aminopyrine, acts similarly to midazole. Although thiocyanate inhibition of H+ secretion is reversed by these weak bases, they only partially reverse the thiocyanate effects on the electrophysiological characteristics of the mucosa. Nitrite inhibition of H+ secretion is not reversed by aminopyrine, but is slightly reversed by imidazole. With Cl--free bathing media, the potential difference (PD) is inverted (the nutrient side becomes negative), and the H+ rate is reduced but still finite and measurable. Under these conditions, thiocyanate abolishes H+ secretion and reduces the magnitude of the inverted PD to about 0, and both imidazole and aminopyrine rapidly reverse the PD to the prethiocyanate level. Thiocyanate does not act as an antagonist but may inhibit H+ secretion by virtue of its action on the molecular machinery. The finding that both imidazole and aminopyrine can reverse this inhibition has the potentiality of providing a much deeper insight into the mechanism of thiocyanate action and into the molecular mechanism of the H+ secretion.