Interaction of ebeinone, an alkaloid from Fritillaria imperialis, at two muscarinic acetylcholine receptor subtypes

Life Sci. 1997;60(8):535-44. doi: 10.1016/s0024-3205(96)00691-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / metabolism
  • Alkaloids / pharmacology*
  • Allosteric Site
  • Animals
  • Guinea Pigs
  • Heart Atria / metabolism
  • Ileum / metabolism
  • In Vitro Techniques
  • Plants / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Muscarinic / classification
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Trachea / metabolism

Substances

  • Alkaloids
  • Receptors, Muscarinic
  • ebeinone