alpha 2-Adrenergic receptor regulation of ion transport in rabbit ileum

Abstract

Catecholamines decrease short-circuit current (Isc), stimulate NaCl absorption, and inhibit HCO3 secretion in rabbit ileal mucosa in vitro. These effects appear to be mediated by .alpha.-adrenergic receptors because they are partially blocked by phentolamine and not by propranolol. To further characterize this receptor system, the interactions of epinephrine (Epi) with .alpha.-subtype-selective antagonists were determined. Prazosin (PZ), a specific .alpha.1-antagonist, did not alter the Epi dose-response curve at concentrations up to 10-5 M. yohimbine (YO), a specific .alpha.2-antagonist, completely inhibited the Epi effect on Isc. At 10-5 M, YO increased by 70-fold the concentration of Epi required to produce a half-maximal effect (ED50; from 1.4 .times. 10-7 M to 10-5 M). YO and PZ by themselves had no significant effect on Isc in concentrations up to 10-5 M. Clonidine, a specific .alpha.2-agonist, decreased Isc with an ED50 similar to that of Epi; its effect was blocked by YO but not by PZ. Two .alpha.1-selective agonists, methoxamine and phenylephrine, only caused a decrease in Isc in doses greater than 10-5 M. This effect was reversed by YO but not by PZ. The effects of YO and PZ on Epi-modified Cl fluxes were also determined. YO completely aborted the effects of Epi on net Cl flux. No significant effects were seen with PZ. The effects of Epi on ileal ion transport are apparently mediated by a specific .alpha.2-adrenergic receptor present in ileal mucosa and that no physiologic .alpha.1-receptor function can be demonstrated.