title: Reserpine up-regulation of rat renal cortical beta adrenergic receptors is independent of its effect on the sympathetic nervous system.
abstract: Experiments were performed to evaluate the mechanism underlying our recent observation that reserpine but not surgical denervation up-regulates rat renal cortical beta adrenergic receptors. The specific binding of [125I]iodocyanopindolol was used to quantitate the beta adrenoceptors. Chronic high-dose guanethidine, which decreased renal tissue and circulating catecholamines to the same extent as reserpine, failed to up-regulate renal beta adrenoceptors, which indicates that the effect of reserpine was not due to changes in the ambient catecholamine concentration. Isoproterenol-stimulated renin secretion, a measure of postsynaptic receptor function, was increased by reserpine but not denervation, which indicates that the failure to observe beta adrenoceptor up-regulation by radioligand binding studies after denervation was not an anomaly caused by loss of presynaptic receptors masking postsynaptic supersensitivity. Reserpine was effective even in denervated kidneys. Up-regulation of renal beta adrenoceptors with reserpine occurred even after destruction of peripheral sympathetic nervous system by a combination of adrenal demedullation and high-dose guanethidine administration. A lower daily dose of reserpine (0.3 mg/kg instead of 0.5 mg/kg), which caused no weight loss, was effective in producing beta adrenoceptor up-regulation. Antagonism of reserpine depletion of nerve terminal norepinephrine by tranylcypromine, a monoamine oxidase inhibitor, did not nullify renal beta adrenoceptor up-regulation. Overall, our results indicate that reserpine up-regulation of renal beta adrenergic receptors is independent of the sympathetic nervous system and possibly is a direct effect.
authors.affiliation: Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York.
authors.forename: T L
authors.initials: TL
authors.lastname: Fortin
authors.forename: P R
authors.initials: PR
authors.lastname: Sundaresan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002395:Catecholamines / Q000097:blood / Q000502:physiology; D006145:Guanethidine / Q000378:metabolism / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D012110:Reserpine; D010869:Pindolol; D006145:Guanethidine