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Relationship between intrinsic activities of agonists in normal and desensitized tissue and agonist-induced loss of beta adrenergic receptors.

The intrinsic activities of 14 agonists at beta adrenergic receptors were determined in membranes prepared from control L6 muscle cells or from cells preincubated in the presence of isoproterenol for 20 min. Several drugs that were full agonists when studied with membranes from naive cells were partial agonists in membranes prepared from desensitized cells. Prolonged incubation of cells with agonists resulted in a 70 to 80% decrease in the density of beta adrenergic receptors. This effect was observed after incubation of cells with either full or partial agonists, suggesting that the extent of receptor loss is independent of the intrinsic activity of an agonist. The rate of receptor loss was related, however, to the intrinsic activity of an agonist. The rate of receptor loss correlated with the intrinsic activities of agonists in desensitized (r = 0.94) and control (r = 0.87) membranes.