Effect of noradrenergic lesions on subtypes of alpha 2-adrenoceptors in rat brain.
The binding of [3H]rauwolscine to alpha 2A- (also referred to as alpha 2D-) and alpha 2C-adrenoceptors in homogenates of rat cerebral cortex was measured by exploiting the selectivity of oxymetazoline for alpha 2A-adrenoceptors. Inhibition of [3H]rauwolscine binding by oxymetazoline was modeled best assuming binding to two sites (p < 0.001). Competition curves for oxymetazoline were shifted rightward by the addition of GTP (250 microM) but were still fit best by a two-site model (p < 0.001). A concentration of oxymetazoline was calculated that would optimally antagonize [3H]rauwolscine binding (with GTP present) to oxymetazoline-sensitive alpha 2A-adrenoceptors, minimally inhibiting binding to alpha 2C-adrenoceptors. Subsequently, [3H]rauwolscine binding to alpha 2A- and alpha 2C-adrenoceptors in cortex was examined 3 weeks after destruction of noradrenergic terminals. Binding to alpha 2C-adrenoceptors was increased significantly after treatment with 6-hydroxydopamine, (6-OHDA) compared with vehicle-treated controls, whereas binding to alpha 2A-adrenoceptors was unchanged. Pretreatment of rats with desipramine before 6-hydroxydopamine, to protect noradrenergic neurons, resulted in no changes in binding to either alpha 2A- or alpha 2C-adrenoceptors. Thus, alpha 2C-adrenoceptors are regulated by changes in synaptic availability of norepinephrine. alpha 2A-Adrenoceptors are either not regulated by synaptic norepinephrine or are located both post- and presynaptically so that up-regulation of postsynaptic alpha 2A-adrenoceptors is offset by a loss of presynaptic alpha 2A-adrenoceptors.
Ordway
G A
GA
Department of Psychiatry, University of Mississippi Medical Center, Jackson 39216-4505.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D015116:5,7-Dihydroxytryptamine; D006160:Guanosine Triphosphate; D016627:Oxidopamine; D010109:Oxymetazoline; D003891:Desipramine