title: Interaction of ebeinone, an alkaloid from Fritillaria imperialis, at two muscarinic acetylcholine receptor subtypes.
abstract: The ability of the alkaloid, ebeinone, isolated from Fritillaria imperialis, to act at muscarinic M2 and M3 acetylcholine receptors was investigated. In functional studies with guinea-pig left atrium, ebeinone was found to be ca. 10-fold more active as an antagonist of responses to carbachol (CCh) than in either guinea-pig ileum or trachea. Estimates of dissociation constants (KB values) in the three tissues were 77.3, 931.1 and 547.0 nM, respectively. Inhibition binding studies in rat atria with the non-selective antagonist [3H]N-methylscopolamine ([3H]NMS) showed ebeinone to have a KI value of 80.9 nM. Comparison of ebeinone with pancuronium, another steroid-like compound with a similar KB value at the muscarinic M2 receptor, found both compounds able to retard the dissociation rate of [3H]NMS in atria, indicating an allosteric mode of interaction at the M2 receptor. It is concluded that ebeinone exhibited a higher affinity for muscarinic M2 receptors than for M3 receptors in the guinea-pig and that it interacted allosterically at rat atrial M2 receptors.
authors.affiliation: Department of Physiology and Pharmacology, Aga Khan University Medical College, Karachi, Pakistan.
authors.forename: A H
authors.initials: AH
authors.lastname: Gilani
authors.forename: F
authors.initials: F
authors.lastname: Shaheen
authors.forename: A
authors.initials: A
authors.lastname: Christopoulos
authors.forename: F
authors.initials: F
authors.lastname: Mitchelson
mesh_terms: D000470:Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D000495:Allosteric Site; D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D010944:Plants / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
chemical_list: D000470:Alkaloids; D011976:Receptors, Muscarinic; C104693:ebeinone