Stimulation of sodium transport in turkey erythrocytes by cyclic 3',5'-AMP.

Abstract

At relatively low concentrations the β-adrenergic blocking agent, propranolol, inhibits competitively isoproterenol-stimulated sodium transport in intact turkey erythrocytes. At higher concentrations propranolol alone inhibits sodium transport; however, this effect is probably not mediated by the adenylate cyclase system. When propranolol was added after turkey erythrocytes had been stimulated by isoproterenol, there was a progressive decrease in sodium influx and an associated decrease in cellular cyclic 3',5'-AMP. These results, plus the observation that addition of cyclic 3',5'-AMP to the medium stimulated sodium transport, offer further support for the conclusion that stimulation of sodium transport in turkey erythrocytes by β-adrenergic catecholamines is mediated by activation of adenylate cyclase and consequent accumulation of cellular cyclic 3'5'-AMP. Our results also illustrate that the relation between total cellular cyclic 3'5'-AMP and sodium transport changes over time suggesting a developing refractoriness to or acompartmentalization of cellular cyclic 3',5'-AMP. Neither theophylline nor caffeine altered sodium transport or potentiated the effect of submaximal concentrations of isoproterenol; however, both methylxanthines inhibited the degradation of extracellular cyclic 3',5'-AMP and potentiated the stimulation of sodium transport by extracellular cyclic nucleotide. These results suggest that in the turkey erythrocyte phosphodiesterase may be located exclusively on the external surface of the erythrocyte membrane and acts only on extracellular cyclic nucleotides. (Endocrinology95: 499, 1974)