[Identification of the cardiac beta-adrenergic receptor protein: solubilization and purification by affinity chromatography].

ABSTRACT A protein that binds catecholamines with a specificity parallel to that of their in vivo effects on cardiac contractility (isoproterenol > epinephrine or norepinephrine > dopamine > dihydroxyphenylalanine) was solubilized from a microsomal fraction of canine ventricular myocardium. The binding protein was purified 500 to 800-fold by solubilization and subsequent affinity chromatography with conjugates of norepinephrine linked to agarose beads. Purified beta-adrenergic binding protein exists in two forms, corresponding to molecular weights of 40,000 and 160,000. The purified material has a single association constant, 2.3 x 10(5) liters/mol (as compared to two association constants, 10(7) and 10(6) liters/mol, for the binding protein in particulate form) but retains the identical binding specificity for beta-adrenergic drugs and antagonists.

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    ABSTRACT: Inflammation in the nervous system is widely recognized as contributing to a number of neurological conditions. However, the central nervous system (CNS) has also been classically recognized as occupying a privileged site with respect to immune-related phenomena. This dichotomy is widely understood to be a functional manifestation of known CNS and peripheral nervous system (PNS) barriers, in addition to the variable immunocompetence of certain CNS and PNS cells. Moreover, the variable capacities of, for example, CNS cells to produce cytokines and/or induce neurotrophic factors in certain disease states or after trauma are also recognized as contributing. In light of these considerations, this chapter explores the damage-to-benefit ratio for several classes of cells and their secretory products after CNS and PNS lesions, trauma, and diseases. Included are an evaluation of macrophage, microglial, and Schwann cell activation, as well as T-lymphocyte responses during several experimental pathophysiological models and disease states. These cellular activities range from being protective to pathogenic factors. The contributions of autoreactive antibodies (Abs) to disease processes and nervous system repair are also considered for their effects that categorically parallel described cellular responses. However, in experimental model systems involving myelination, overall observations point to Abs synthesized following CNS injuries as being potentially therapeutic, and these examples are reviewed. Moreover, data presented from the studies of cytokines in experimental and natural disease states demonstrate that certain cytokines have the capacity to generate multiple and opposite effects including producing damage, protection, or regeneration. Examples are described involving tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and interferon (IFN)-γ. Ultimately, our understanding of the inflammatory processes that protect versus those that contribute to neuronal damage will be a prerequisite to designing effective new therapies for diseases affecting the nervous system.
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    ABSTRACT: Isoproterenol, norepinephrine, and epinephrine covalently bound to glass beads exert a positive inotropic effect on isometrically contracting papillary muscles from cats. Immobilized isoproterenol maintains increases in force and velocity of contraction for more than 5 hr. 1 muM Cocaine potentiates the action of immobilized norepinephrine, isoproterenol, and epinephrine, but not of isoproterenol in solution. The data presented indicate that the effects of immobilized catecholamines are not due to their coming off the glass. The effects observed with cocaine and immobilized catecholamines are not altered by prior treatment of the muscle with reserpine. These results suggest that the major site of catecholamine action is on receptors located on the extended surface of myocardial cells and a post-junctional site for cocaine potentiation.
    Proceedings of the National Academy of Sciences 05/1973; 70(4):1214-7. · 9.67 Impact Factor
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    ABSTRACT: New physiologic insights are being provided by studies of isolated hormone receptors. Clinical implications of this research fall into two general categories: the use of isolated receptors as tools for measurement of hormones in biologic fluids, and potential insights into the mechanisms of a variety of pathologic states. Hormone receptors share both high affinity and great specificity of binding. These qualities permit isolated receptors to be used for a new form of competitive radiodisplacement assay that is in many ways analogous to radioimmunoassay. It differs, however, in that receptors, rather than antibodies, are used to bind the radioactively labeled substance. The most recent and potentially exciting clinical application of research on isolated hormone receptors is the possibility of gaining new understanding of the pathophysiology of a variety of pathologic states. These all have in common an abnormal sensitivity to one or another hormonal substance. Alterations in receptor affinity or number, or in the coupling of receptors to more distal cellular processes, could well explain these altered states of hormone responsiveness.
    New England Journal of Medicine 06/1973; 288(20):1061-6. DOI:10.1056/NEJM197305172882009 · 55.87 Impact Factor
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