[3H]cytisine binding to nicotinic cholinergic receptors in brain.
Cytisine, a ganglionic agonist, competes with high affinity for brain nicotinic cholinergic receptors labeled by any of several nicotinic 3H-agonist ligands. Here we have examined the binding of [3H]cytisine in rat brain homogenates. [3H]Cytisine binds with high affinity (Kd less than 1 nM), and specific binding represented 60-90% of total binding at all concentrations examined up to 15 nM. The nicotinic cholinergic agonists nicotine, acetylcholine, and carbachol compete with high affinity for [3H]cytisine binding sites, whereas among nicotinic receptor antagonists only dihydro-beta-erythroidine competes with high affinity (in the nanomolar range). Comparison of binding in several brain regions showed that [3H]cytisine binding is higher in the thalamus, striatum, and cortex than in the hippocampus, cerebellum, or hypothalamus. The pharmacology and brain regional distribution of [3H]cytisine binding sites are those predicted for neuronal nicotinic receptor agonist recognition sites. The high affinity and low nonspecific binding of [3H]cytisine should make it a very useful ligand for studying neuronal nicotinic receptors.
Pabreza
L A
LA
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007.
Dhawan
S
S
Kellar
K J
KJ
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001392:Azocines; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D011807:Quinolizines; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014316:Tritium; D000093843:Quinolizidine Alkaloids
D000109:Acetylcholine; D000470:Alkaloids; D001392:Azocines; D002217:Carbachol; D009538:Nicotine; D011807:Quinolizines; D011978:Receptors, Nicotinic; D014316:Tritium; C004712:cytisine; D000093843:Quinolizidine Alkaloids