[alpha]1-Adrenoceptors antagonize activated chloride conductance of amphibian skin epithelium

The effects of adrenoceptor agonists on the transepithelial Cl^sup -^ conductance (G^sup Cl^) in the skin of several amphibian species, both toads and frogs, were studied. Epinephrine (Epi) from the serosal side selectively and reversibly inhibited the voltage-activated G^sup Cl^ in toad skin and the short-circuit G^sup Cl^ in frog skin. The main effects of activation of the adrenoceptors must reside in the skin epithelium and not in the glands, since measurements were made both from intact skins and split epithelia with essentially the same results. Effective concentrations of Epi were variable among individual tissues. G^sup Cl^ was reduced to 34±17% (n=46) with 1 µmol/l Epi, but in some tissues 0.1 µmol/l inhibited more than 80% of G^sup Cl^, whereas some preparations were little influenced at >3 µmol/l Epi. The affected receptor type was identified by the use of the α^sub 1^-agonist phenylephrine, which mimicked the response of Epi at concentrations above 30 µmol/l, whereas the α^sub 2^-agonists xylazine and iodoclonidine had no effect at supramaximal concentrations. Prazosin, a specific α^sub 1^-antagonist, reduced or eliminated the inhibition by Epi, but the response pattern suggests a low affinity. The α^sub 2^-antagonist yohimbine, at concentrations ≤0.3 µmol/l, had a minimal effect, but reduced the inhibition by Epi at concentrations of 1-10 µmol/l. This might indicate affinity to α^sub 1^-adrenoceptors in amphibian skin. Activation of β-adrenoceptors by isoproterenol (0.1-5 µmol/l) led to a transient increase of the baseline inactivated component of G^sup Cl^ with a slight reduction of the voltage-activated G^sup Cl^ at the higher concentrations, but the inhibitory effect of Epi was not altered. Epi, on the other hand, neither prevented nor reversed the induction of a voltage-insensitive G^sup Cl^ in toad skin caused by application of cAMP at supramaximal concentrations (>100 µmol/l CPT-cAMP). Preincubation of the serosal medium with Ca^sup 2+^-free solution (in the presence of 2 mmol/l EGTA) for extended periods of time (>30 min) eliminated the response to Epi. It is concluded that α^sub 1^-adrenoceptors participate in the physiological control of voltage-activated Cl^sup -^ conductance in amphibian skin epithelium via modulation of intracellular Ca^sup 2+^, presumably by efflux from intracellular stores.[PUBLICATION ABSTRACT]