TY - JOUR
T1 - Interaction of ebeinone, an alkaloid from Fritellaria imperialis, at two muscarinic acetylcholine receptor subtypes
AU - Gilani, A. H.
AU - Shaheen, F.
AU - Christopoulos, A.
AU - Mitchelson, F.
PY - 1997/1/17
Y1 - 1997/1/17
N2 - 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.
AB - 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.
KW - allosteric interaction
KW - ebeinone
KW - muscarinic acetylcholine receptors
KW - pancuronium
UR - http://www.scopus.com/inward/record.url?scp=0031575396&partnerID=8YFLogxK
U2 - 10.1016/S0024-3205(96)00691-1
DO - 10.1016/S0024-3205(96)00691-1
M3 - Article
C2 - 9042388
AN - SCOPUS:0031575396
SN - 0024-3205
VL - 60
SP - 535
EP - 544
JO - Life Sciences
JF - Life Sciences
IS - 8
ER -