Showing papers by "Robert J. Lefkowitz published in 1973"

Binding of catecholamines to receptors in cultured myocardial cells.

Abstract: THE inotropic and chronotropic effects of catecholamines on cardiac tissue are mediated by binding to specific β-adrenoeeptor sites1, activation of the enzyme adenyl cyclase2 and generation of the “second messenger” cyclic AMP3. Sites have been identified in subcellular membrane fragments from mammalian cardiac4–8, hepatic9,10, erythrocytic11 and splenic capsular tissue12 which bind radioactively labelled catecholamines with specificity and other characteristics to be expected of physiological β-adrenoceptors. These sites seem to be proteins7,10 and have been partially purified5,10.

Isolated hormone receptors: physiologic and clinical implications.

Abstract: DURING the past decade, the many and varied roles of the "second-messenger" cyclic AMP have become better understood1 Figure 1, based on the work of Sutherland et al,2 shows how hormones act on cyclic AMP In this scheme, hormones that circulate in blood are the "first messengers" They interact with the enzyme adenyl cyclase in the plasma membranes of their target tissues, leading to the conversion of ATP to cyclic AMP, which then exerts the characteristic effects of the particular hormone One of the intriguing features of this sequence is that it is, on the one hand, so general, and, on

Physiological receptors as physicochemical entities.

Abstract: Recent advances in the identification and isolation of cell-membrane hormone receptors are reviewed and critically evaluated. Three systems are examined in some detail: the isolated adrenergic, cholinergic, and insulin binding sites. A physiological receptor performs two important functions: specific binding of biologically active drugs and hormones, and activation of subsequent cellular processes such as adenyl cyclase or sodium ion permeability. In each of the three systems discussed, a binding site thought to represent the physiological receptor has been solubilized and partially purified. These binding sites appear to be macromolecules, generally proteins located within the plasma membranes of sensitive cells. They bind agonist and antagonist drugs rapidly and reversibly, with specificities and affinities generally parallel to those characterizing the interaction of these compounds with intact tissues in vivo. To date, only the binding characteristics of these isolated receptor sites have been studied, and little is known of their effector properties. Firm proof that the sites being studied are in fact identical with the physiological receptors will require their recombination with other cell-membrane constituents form intact systems in which addition of agonist drugs is followed not only by binding, but also by a characteristic biological response.