Effects of Higenamine on Regulation of Ion Transport in Guinea Pig Distal Colon

Abstract

Effects of higenamine on Na⁺, K⁺ and Cl^- transport were studied on stripped guinea pig distal colonic mucosa in vitro using Ussing chambers. Addition of 10^-5M higenamine induced a biphasic change in short circuit current (Isc): a transient increase followed by a long-lasting decrease that was accompanied by an increase in transepithelial conductance (Gt). The initial phase with an increase in Isc was partially inhibited by serosal bumetanide and abolished by mucosal diphenylamine-2-carboxylate, a chloride channel blocker, indicating transient induction of Cl^- secretion. The second phase with a decrease in Isc was composed of two effects: the inhibition of the amiloride-sensitive electrogenic Na⁺ absorption and the stimulation of the bumetanide-sensitive K⁺ secretion. However, the initial transient increase was not observed at the lower concentration of higenamine (10^-8−10^-6M). All the changes in Isc and Gt induced by higenamine were suppressed by the non-selective β-adrenergic receptor antagonist propranolol and by the β₂-adrenergic receptor antagonist ICI-118, 551, but not by the β₁-adrenergic-receptor-selective antagonist atenolol or by the α-antagonists phentolamine, prazosin and yohimbine. These results suggest that higenamine inhibits electrogenic Na⁺ absorption and stimulates electrogenic K⁺ and Cl^- secretion through β₂-adrenergic receptors in guinea pig distal colon.