Time course of changes in [3H]prazosin binding after catecholaminergic denervation by 6-hydroxydopamine in rat cerebral cortex. Inhibitory effects of ascorbic acid on the alpha 1-adrenoceptor.
The binding of [3H]prazosin to alpha 1-adrenoceptors was studied in membranes isolated from the rat cerebral cortex, at different times after the intraventricular injection of 6-hydroxydopamine. In controls, the binding was saturable with the Bmax = 113 pmol/g protein and KD = 0.93 nM, and revealed a single class of sites. After the action of the neurotoxin there was an increase in binding that reached +68% after 7 days and +35% after 14 days. This effect corresponded to an increase in Bmax (190 pmol/g protein) and a decrease in affinity (Kd = 2.1 nM), at 7 days after 6-hydroxydopamine. Carrying on experiments without ascorbic acid in the diluent, the well known inhibitory effect in vitro, that this drug has on the binding of several receptor ligands, was confirmed in vivo. The results obtained suggest that the noradrenergic denervation produced by the neurotoxin is capable of inducing adaptive changes, in alpha 1-post-synaptic adrenoceptors as measured by the binding of [3H]prazosin.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000502:physiology; D003000:Clonidine / Q000378:metabolism; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016627:Oxidopamine; D011224:Prazosin / Q000378:metabolism*; D011799:Quinazolines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D013997:Time Factors
D002395:Catecholamines; D006892:Hydroxydopamines; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D016627:Oxidopamine; D003000:Clonidine; D001205:Ascorbic Acid; D011224:Prazosin