α Adrenergic receptors in rat parotid cells. II. Desensitization of receptor binding sites and potassium release

Preincubation of dissociated rat parotid acinar cells with the α-adrenergic agonist epinephrine produced a time- and concentration-dependent decrement in the α-adrenergic response of the cells, K+ release. This receptor desensitization by epinephrine was specific for the α-adrenergic receptor of the acinar cells, since K+ release by the muscarinic cholinergic agonist carbachol remained unchanged. The half-time for desensitization was 2 min at 38°. Chelation of Ca2+ with ethylene glycol bis(β-aminoethyl ether)N,N'-tetraacetic acid prevented epinephrine-induced K+ release, but did not prevent desensitization. The α-adrenergic antagonist phentolamine did not produce desensitization, but blocked the desensitization caused by epinephrine. Desensitized cells slowly resensitized when incubated in the absence of agonist. Depolarization of the acinar cell membrane potential by elevating external K+ concentration or incubating in ouabain markedly accelerated resensitization. Desensitization and resensitization of the α-adrenergic biological response were accompanied by parallel changes in the α-adrenergic receptor binding sites assessed by [3H]-dihydroergocryptine binding. These data are the first demonstration of α-adrenergic receptor desensitization. In rat parotid acinar cells, rapid alterations in membrane binding sites contribute to desensitization and resensitization of the α-adrenergic response and, as in the cholinergic receptor of muscle, the membrane voltage appears to regulate the rate of receptor resensitization.

Duke Scholars

Author Robert J. Lefkowitz Medicine, Cardiology

Author Warren James Strittmatter Neurology, Behavioral Neurology