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

A. H. Gilani, F. Shaheen, A. Christopoulos, F. Mitchelson

Research output: Contribution to journalArticleResearchpeer-review

62 Citations (Scopus)

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 response to carbachol (CCh) than in either guinea-pig ileum or trachea. Estimates of dissociation constants (K(B) 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 K1 value of 80.9 nM. Comparison of ebeinone with pancuronium, another steroid-like compound with a similar K(B) 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.

Original languageEnglish
Pages (from-to)535-544
Number of pages10
JournalLife Sciences
Volume60
Issue number8
DOIs
Publication statusPublished - 17 Jan 1997

Keywords

  • allosteric interaction
  • ebeinone
  • muscarinic acetylcholine receptors
  • pancuronium

Cite this

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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 response to carbachol (CCh) than in either guinea-pig ileum or trachea. Estimates of dissociation constants (K(B) 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 K1 value of 80.9 nM. Comparison of ebeinone with pancuronium, another steroid-like compound with a similar K(B) 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.",
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Interaction of ebeinone, an alkaloid from Fritellaria imperialis, at two muscarinic acetylcholine receptor subtypes. / Gilani, A. H.; Shaheen, F.; Christopoulos, A.; Mitchelson, F.

In: Life Sciences, Vol. 60, No. 8, 17.01.1997, p. 535-544.

Research output: Contribution to journalArticleResearchpeer-review

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