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In a review article, Holton (1) states that both alpha and beta agonists in doses of the order of 1 mcg kg-' min-I inhibit acid secretion in conscious animals, that histamine-stimulated secretion is less easily depressed than other means such as pentagastrin stimulation, and that beta agonists in doses of the order of 0.1-0.5 mcg kg-' min-' increase histamine-stimulated secretion. However, much of the influence of adrenergic amines, in vivo, had been attributed to effects on mucosal blood flow (2). The isolated frog gastric mucosa enables the effects of catecholamines to be studied in the absence of a blood supply. Thorpe et al. (3) had, in fact, investigated the effects of catecholamines on the H+ secretory rate of the isolated bullfrog gastric mucosa. They found that epinephrine and norepinephrine in concentrations as high as 5 mM produced statistically insignificant decreases in histamine-stimulated H+ secretion. Recently Rose et al. (4) found that norepinephrine, when added to the nutrient solution of isolated gastric mucosae of Rana pipiens, produced a significant decrease of about 20% to about 100% respectively for concentrations increasing from 0.1 to about 2.3 mM. In the case of 5 mM isoproterenol, a beta agonist, Thorpe et a1 found that the H+ secretory rate was significantly decreased by 55% and 60% respectively for histamine and acetylcholine-stimulated H+ secretion. This inhibition of isoproterenol was blocked by propranolol, a beta antagonist. The authors suggested on the basis of their data that isoproterenol inhibited acid secretion by direct activation of mucosal beta-adrenergic receptors. Recent work in our laboratory ( 5 ) lends support to their experimental findings on beta adrenergic amines.In the study of Thorpe et al. (3), however, only the H+ secretory rate was measured. The present investigation considers the inhibitory effects of isoproterenol (Isuprel) , a beta agonist ; epinephrine (Adrenalin) a predominantly beta agonist; and propranolol (Inderal), a beta antagonist on the transmucosal resistance, the transmucosal potential difference (PD) and the H+ secretory rate of the gastric mucosa of Rana pipiens in C1-media. In addition, blocking effects between propranolol and isoproterenol and between propranolol and epinephrine are reported.Methods. The experiments were performed on gastric mucosae of Rana pipiens with an in vitro method described in detail elsewhere (6). Two pairs of electrodes were used, one for sending current across the mucosa and the other for measuring the PD. The resistance was obtained as the change in PD per unit of applied current. The H+ secretory rate was determined by the pH stat method introduced by Durbin and Heinz (7). The pH of the secretory side was maintained at 4.90. The nutrient bathing solution contained (in mMj: Na+, 102; K+, 4; Ca2+, 1; Mg2+, 0.8; 81; 25; phosphate, 1 .O; and glucose,10; and the secretory bathing solution contained: Na+, 102; K+, 4; C1-, 106. Both sides of the mucosa were gassed with 95% O2 and 5% CO,. Histamine was added to the nu...

Experiments were performed on gastric mucosae of Rana pipiens with an in vitro method. Bathing both sides of the mucosae in Cl--free solutions resulted in an inverted potential difference (PD) (i.e., nutrient negative). Cimetidine in a concentration of 10(-4) or 10(-3) M in the nutrient solution gave a positive PD when the H+ secretory rate was zero or near zero and confirmed that the PD versus H+ rate was linear. the origins of the positive PD were examined by ion replacement, e.g., choline for Na+ in both solutions. When both solutions had 25 mM HCO(-)3 (i.e., no HCO(-)3 gradient), the difference in PD between choline sulfate and Na2SO4 solutions indicated a possible small active transport of Na+ from the secretory to nutrient side. Similar experiments indicated no active K+ transport. A residual PD occurred without Na+. With H+ rate zero, 100% O2, and no HCO(-)3, a base secretion of about 0.4 mueq.h-1.cm-2 was obtained in a direction to contribute to the positive PD. Active SO2(-)4 transport may occur.

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