Reserpine up-regulation of rat renal cortical beta adrenergic receptors is independent of its effect on the sympathetic nervous system.
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.
Fortin
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TL
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York.
Sundaresan
P R
PR
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
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D012110:Reserpine; D010869:Pindolol; D006145:Guanethidine