ALPHA(1)-ADRENOCEPTORS ANTAGONIZE ACTIVATED CHLORIDE CONDUCTANCE OF AMPHIBIAN SKIN EPITHELIUM

The effects of adrenoceptor agonists on the transepithelial Cl- conduc tance (G(Cl)) in the skin of several amphibian species, both toads and frogs, were studied. Epinephrine (Epi) from the serosal side selectiv ely and reversibly inhibited the voltage-activated G(Cl) in toad skin and the short-circuit G(Cl) in frog skin. The main effects of activati on of the adrenoceptors must reside in the skin epithelium and not in the glands, since measurements were made both from intact skins and sp lit epithelia with essentially the same results. Effective concentrati ons of Epi were variable among individual tissues. G(Cl) was reduced t o 34+/-17% (n=46) with 1 mu mol/l Epi, but in some tissues 0.1 mu mol/ l inhibited more than 80% of G(Cl), whereas some preparations were lit tle influenced at >3 mu mol/l Epi. The affected receptor type was iden tified by the use of the alpha(1)-agonist phenylephrine, which mimicke d the response of Epi at concentrations above 30 mu mol/l, whereas the alpha(2)-agonists xylazine and iodoclonidine had no effect at suprama ximal concentrations. Prazosin, a specific alpha(1)-antagonist, reduce d or eliminated the inhibition by Epi, but the response pattern sugges ts a low affinity. The alpha(2)- antagonist yohimbine, at concentratio ns less than or equal to 0.3 mu mol/l, had a minimal effect, but reduc ed the inhibition by Epi at concentrations of 1-10 mu mol/l. This migh t indicate affinity to alpha(1)-adrenoceptors in amphibian skin. Activ ation of beta-adrenoceptors by isoproterenol (0.1-5 mu mol/l) led to a transient increase of the baseline inactivated component of G(Cl) wit h a slight reduction of the voltage-activated G(Cl) at the higher conc entrations, but the inhibitory effect of Epi was not altered. Epi, on the other hand, neither prevented nor reversed the induction of a volt age-insensitive G(Cl) in toad skin caused by application of cAMP at su pramaximal concentrations (>100 mu mol/l CPT-cAMP). Preincubation of t he serosal medium with Ca2+-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 alpha(1)-adrenoceptors participate in the physiological control of voltage-activated Cl- conductance in amphibi an skin epithelium via modulation of intracellular Ca2+, presumably by efflux from intracellular stores.