The beta adrenergic receptors of chromatophores of the frog, Rana pipiens

The isolated skin of Rana pipiens was found to be a suitable model for the quantitative study of chromatophore beta adrenergic receptors uninfluenced by prejunctional phenomena. Cumulative concentration-response curves for adrenergic agonists were obtained in preparations in which effective alpha adrenergic blockade had been produced with phenoxybenzamine. The beta adrenergic agonists darkened the preparation, as did melanocyte-stimulating hormone, but the maximum effects differed. The maximum of the l-isoproterenol cumulative concentration-response curve was approximately 50% less than that of melanocyte-stimulating hormone, while the maxima for l-epinephrine and l-norepinephrine were significantly less than that for isoproterenol. Microscopic examination revealed a qualitative difference: while maximal darkening produced by melanocyte-stimulating hormone was associated with maximal changes in both interspot melanophores and iridophores, maximal adrenergic-induced darkening was associated with maximal iridophore granule concentration only. No qualitative differences could be observed in the darkening caused by the three adrenergic agonists. The beta adrenergic potencies of l-norepinephrine and l-isoproterenol relative to l-epinephrine were determined by four-point bioassay. Isoproterenol was found to be 138 times as potent as epinephrine, while norepinephrine was 4 times as potent. Similarly, antagonism of isoproterenol-induced darkening of phenoxybenzamine-pretreated skin samples by the beta adrenergic blocking agents dl-propranolol, dl-sotalol, dl-practolol, l-butoxamine and d-butoxamine was studied, and their KB and pA2 values, respectively, were found to be: dl-propranolol (1.44 X 10(-8)M, 7.81); dl-sotalol (7.25 X 10(-8)M, 7.23); l-butoxamine (6.92 X 10(-6)M, 5.10); dl-practolol (1.91 X 10(-5)M, 4.96); d-butoxamine (no activity). Comparison of the potency ratios and pA2 values cited above with similar parameters obtained by other investigators in several mammalian tissues suggests that there is wide variation among beta adrenergic receptors.