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Antimuscarinic action of liriodenine, isolated from Fissistigma glaucescens , in canine tracheal smooth muscle
Author(s) -
Lin ChienHuang,
Yang ChuenMao,
Ko FengNien,
Wu YangChang,
Teng CheMing
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17161.x
Subject(s) - methoctramine , pirenzepine , schild regression , muscarinic acetylcholine receptor , muscarinic acetylcholine receptor m3 , antagonist , competitive antagonist , chemistry , receptor antagonist , antagonism , contraction (grammar) , muscarinic acetylcholine receptor m2 , receptor , medicine , endocrinology , stereochemistry , pharmacology , biology , biochemistry
1 The antimuscarinic properties of liriodenine, isolated from Fissistigma glaucescens , were compared with methoctramine (cardioselective M 2 antagonist) and 4‐diphenylacetoxy‐ N ‐methylpiperidine (4‐DAMP, smooth muscle selective M 3 antagonist) by radioligand binding tests, functional tests and measurements of second messenger generation in canine cultured tracheal smooth muscle cells. 2 Liriodenine, pirenzepine, methoctramine and 4‐DAMP displaced [ 3 H]‐N‐methyl scopolamine ([ 3 H]‐NMS) binding in a concentration‐dependent manner with K i values of 2.2 ± 0.4 × 10 −6 , 3.3 ± 0.7 × 10 −7 , 8.9 ± 2.3 × 10 −8 and 2.3 ± 0.6 × 10 −9 m , respectively. The curves for competitive inhibition of [ 3 H]‐NMS with liriodenine, methoctramine and 4‐DAMP were best fitted according to a two site model of binding, but pirenzepine was best fitted according to a model with one site. 3 Liriodenine and 4‐DAMP displayed a high affinity for blocking tracheal contraction (p K B = 5.9 and 9.1, respectively) and inositol phosphate formation (p K h = 6.0 and 8.9, respectively), but a low affinity for antagonism of cyclic AMP inhibition (p K B = 4.7 and 7.8, respectively). 4 Methoctramine blocked cyclic AMP inhibition with a high affinity (p K B = 7.4), but it antagonized tracheal contraction and inositol phosphate formation with a low affinity (p K h = 6.1 and 6.0, respectively). 5 In conclusion, both M 2 and M 3 muscarinic receptor subtypes coexist in canine tracheal smooth muscle and are coupled to the inhibition of cyclic AMP formation and phosphoinositide breakdown, respectively. The antimuscarinic characteristics of liriodenine are similar to those of 4‐DAMP. It may act as a selective M 3 receptor antagonist in canine tracheal smooth muscle.