The sympathetic nervous system releases norepinephrine and neuropeptide Y locally from nerve terminals, and epinephrine from the adrenal medulla, transmitters which can bind to specific receptors localized in the heart. The mechanism of sympathetic activation in heart is dependent on the type and density of receptors present on specific cell types, receptor availability to extracellular agonist concentration, and the coupling of receptors to intracellular second messengers. Autoradiographic techniques have identified important differences in beta adrenergic receptor subtype, number and affinity on cardiac myocytes, blood vessels and conduction system.
The first aim of this proposal is to localize alpha adrenergic and neuropeptide Y receptors in myocytes, blood vessels and conduction system thus expanding current knowledge regarding beta receptors to other receptors responsive to sympathetic transmitters. Evidence suggests that a cell responds to alterations in sympathetic input by regulating the number and/or affinity of the post-synaptic receptor.
The second aim of this proposal is to determine if beta adrenergic receptors on myocytes, arterioles and arteries respond to alterations in agonist concentration in a similar manner. This will be done by using autoradiographic evaluation of beta receptor number, agonist affinity and subtype in these tissues. Correlative biochemical measurements of beta receptors and adenylate cyclase activity will be made on membranes from the myocardium and the large coronary arteries.
The third aim of this proposal will test the hypothesis that altering local agonist concentration redistributes beta adrenergic receptors within the cardiac myocyte, extending knowledge of beta receptor localization to the subcellular level. Agonist concentration will be altered acutely or chronically, followed by electron microscopic localization of the beta receptor. Correlative biochemical measurements of beta adrenergic receptors and adenylate cyclase will be made on subcellular fractions of heart homogenates. Alterations in the sympathetic nervous system have been implicated in the pathology of disease states such as hypertension, myocardial infarction and heart failure. These studies will provide unique information regarding the localization of adrenergic and NPY receptors, knowledge which may be applicable to those diseases.
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| Mumby, S M; Muntz, K H (1995) Receptor regulation of G protein palmitoylation. Biochem Soc Trans 23:156-60 |
| Zhao, M; Muntz, K H (1993) Differential downregulation of beta 2-adrenergic receptors in tissue compartments of rat heart is not altered by sympathetic denervation. Circ Res 73:943-51 |
| Muntz, K H (1992) Autoradiographic characterization of beta-adrenergic receptor subtype in the canine conduction system. Circ Res 71:51-7 |
