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Mechanism of xanthine‐induced relaxation of guinea‐pig isolated trachealis muscle
Author(s) -
Ogawa K.,
Takagi K.,
Satake T.
Publication year - 1989
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.1476-5381.1989.tb11983.x
Subject(s) - trachealis muscle , xanthine , chemistry , theophylline , muscle relaxation , guinea pig , medicine , endocrinology , ibmx , muscle contraction , stereochemistry , biochemistry , biology , enzyme , membrane potential , charybdotoxin , in vitro , forskolin
1 Four 3‐alkylxanthines (3‐methylxanthine, 3‐n‐propylxanthine (enprofylline), 3‐n‐butylxanthine and 3‐iso‐butylxanthine) and four 1‐methyl‐3‐alkylxanthines (1‐methyl‐3‐methylxanthine (theophylline), 1‐methyl‐3‐n‐propylxanthine, 1‐methyl‐3‐n‐butylxanthine and 1‐methyl‐3‐iso‐butylxanthine (IBMX)), were compared in terms of cyclic AMP phosphodiesterase (PDE) inhibition and trachealis muscle relaxation. The relationship between xanthine structure and cyclic AMP PDE inhibition was also studied. 2 Xanthine induced relaxation of guinea‐pig isolated trachealis muscle was measured against spontaneous tone. 3 The four 1‐methyl‐3‐alkylxanthines were each significantly more potent than the corresponding 3‐alkylxanthines in relaxing the isolated trachealis muscle. The 1‐methyl‐3‐alkylxanthines were similarly more potent than the corresponding 3‐alkyl derivatives in inhibiting low K m cyclic AMP PDE. There was a strong positive correlation between low K m cyclic AMP PDE inhibition and the tracheal smooth muscle relaxation evoked by the xanthine derivatives. 4 Since methylation of the 1‐position of each 3‐alkylxanthine increased the potency of the derivative in inhibiting low K m cyclic AMP PDE and in relaxing trachealis muscle and since a strong positive correlation was observed between the relaxant EC 50 and the K i value of each xanthine derivative, it is suggested that low K m cyclic AMP PDE inhibition by xanthines plays an important role in their tracheal relaxant effect.