Receptor binding and functional evidence suggest that postsynaptic alpha 2-adrenoceptors in rat brain are of the alpha 2D subtype.
This study has determined the subtype(s) of postsynaptic alpha 2-adrenoceptors in rat brain. This question has been addressed by using two separate approaches, i.e. ligand displacement of [3H]2-(2-methoxy)-1,4-benzodioxan-2-yl)-2-imidazoline ([3H]RX 821002) from membranes prepared from rat cortex after noradrenergic denervation and, secondly, by antagonism of clonidine-induced mydriasis. After rats had been lesioned using N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 100 mg/kg i.p., 30 min after zimeldine 10 mg/kg i.p.), noradrenaline was undetectable in the cortex 3 days later. Displacement of [3H]RX 821002 with a range of agonists and antagonists which distinguish between the known alpha 2-adrenoceptor subtypes (alpha 2A-2D) yielded pKi values which correlated very well with reported values for the alpha 2D-adrenoceptor (r = 0.929; P < 0.001), but not the alpha 2A (r = 0.450; P = 0.192), alpha 2B (r = 0.280, P = 0.434) or alpha 2C (r = 0.283; P = 0.460) subtypes. Similarly, the potencies of various alpha 2-adrenoceptor antagonists to inhibit clonidine (0.03 mg/kg i.p.)-induced mydriasis in conscious rats correlated strongly with their pKi values for alpha 2D-adrenoceptors (r = 0.899; P = 0.015) but not alpha 2A-(r = 0.369; P = 0.472), alpha 2B-(r = -0.224; P = 0.670) or alpha 2C-adrenoceptors (r = 0.253; P = 0.584). These data are, therefore, consistent and argue strongly that postsynaptic alpha 2-adrenoceptors in the rat cortex and Edinger-Westphal nucleus are of the alpha 2D subtype.
D018663:Adrenergic Agents / Q000633:toxicity; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001596:Benzylamines / Q000633:toxicity; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000633:toxicity; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D019329:Idazoxan / Q000031:analogs & derivatives; D008297:Male; D015878:Mydriasis / Q000139:chemically induced / Q000188:drug therapy*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015031:Zimeldine / Q000633:toxicity
D018663:Adrenergic Agents; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001596:Benzylamines; D004146:Dioxanes; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; D015031:Zimeldine; C058525:2-methoxyidazoxan; D003000:Clonidine; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine; D019329:Idazoxan