The overall goal of this research program is to increase our understanding of the factors involved in the regulation of receptors for autonomic neurotransmitters and hormones. These studies are designed to investigate autoradiographically the localization of Alpha1-, Beta1-, and Beta2-adrenergic receptors in rat kidney and to characterize the biochemical and physiological response to stimulation of each of these receptors. The effects of altered levels of stimulation on the density and properties of these receptors will be determined. Additionally, the functional significance of such alterations will be studied by measuring the biochemical and physiological response to the stimulation of each of these receptors in kidney preparations from control and treated rats. In particular, isoproterenol-stimulated adenylate cyclase activity and norepinephrine-stimulated phosphatidylinositol breakdown will be characterized and utilized as measures of the biochemical response to activation of Beta- and Alpha1-adrenergic receptors, respectively. Similarly, isoproterenol-stimulated renin release or norepinephrine-stimulated, prazosin-inhibitable inhibition of renin release from slices of kidney or isolated glomeruli will be characterized and utilized as physiological correllates of Beta and Alpha1-adrenergic receptor stimulation, respectively. The degree of receptor stimulation will be altered utilizing the chronic administration of several commonly used therapeutic interventions. Thus, Beta-receptor stimulation will be decreased by the administration of propranolol or pindolol, the latter possessing a significant degree of intrinsic sympathomimetic activity, as well as the administration of a Beta1- or a Beta2-selective antagonist. These studies are designed to examine the possibility that the subtypes of renal Beta-adrenergic receptors can be independently regulated and to determine the functional consequences of such selective regulation. Stimulation of Alpha1-adrenergic receptors will be decreased by the administration of prazosin and the functional consequences of this will be determined. Receptor stimulation will be increased by the chronic administration of several types of antidepressants as well as the direct administration of catecholamines. The effects on receptor density will be determined autoradiographically at high anatomical resolution. Additionally, the effects on the functional correllates of these binding sites will be determined for each receptor type.
| Vos, P; Kaufmann, D; Hand, P J et al. (1990) Beta 2-adrenergic receptors are colocalized and coregulated with ""whisker barrels"" in rat somatosensory cortex. Proc Natl Acad Sci U S A 87:5114-8 |
| Vos, P; Davenport, P A; Artymyshyn, R P et al. (1987) Selective regulation of beta-2 adrenergic receptors by the chronic administration of the lipophilic beta adrenergic receptor agonist clenbuterol: an autoradiographic study. J Pharmacol Exp Ther 242:707-12 |
