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

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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title = "Interaction of ebeinone, an alkaloid from Fritellaria 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 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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