Time-course in binding of [3H]dihydroergokryptine to total alpha and alpha1 adrenoceptors of cerebral cortex of rat after denervation by 6-hydroxydopamine.
In control rats and in rats after intraventricular injection of 6-hydroxydopamine, the total specific binding of [3H]dihydroergokryptine to membranes of the cerebral cortex was studied. The time course of the catecholaminergic denervation in its influence on total alpha-adrenoceptors, and on the binding to alpha 1-receptors was followed, after blocking the alpha 2, with yohimbine. Using displacement curves, 5 X 10(-7) M was determined as the concentration of yohimbine needed to differentiate alpha 1 from alpha 2-adrenoceptors. In control rats, the total binding showed a Bmax of 300 pmol/g protein and a KD of 1.9 nM with a single type of binding site. The binding of [3H]dihydroergokryptine that was not displaced by yohimbine represented about 70% of the total. Denervation by 6-hydroxydopamine produced, after two days, a decrease in total binding (P less than 0.01), followed by a progressive increase, that reached 41% above the control after 22 days (P less than 0.1). The alpha 1-sites were reduced after two days and later increased to reach 63% above the control (P less than 0.01) at 22 days. These results suggest that after catecholaminergic denervation there is an increase in total alpha-adrenoceptors and in alpha 1-receptors in membranes of the cerebral cortex. These changes could be correlated with a possible post-synaptic supersensitivity after denervation.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D015016:Yohimbine; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine