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3‐Aminopropylphosphinic acid—a potent, selective GABA B receptor agonist in the guinea‐pig ileum and rat anococcygeus muscle
Author(s) -
Hills Judith M.,
Dingsdale Rhona A.,
Parsons Michael E.,
Dolle Roland E.,
Howson William
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.tb12591.x
Subject(s) - baclofen , agonist , ileum , bicuculline , gabab receptor , medicine , endocrinology , chemistry , guinea pig , muscle contraction , pharmacology , biology , gabaa receptor , receptor
1 3‐Aminopropylphosphinic acid, a γ‐aminobutyric acid (GABA) analogue, was tested for activity on guinea‐pig isolated ileum and rat isolated anococcygeus muscle preparations. The effects of 3‐aminopropylphosphinic acid were compared with those of GABA and baclofen. 2 In the electrically stimulated ileum, 3‐aminopropylphosphinic acid, like GABA and baclofen, caused a concentration‐dependent inhibition of the cholinergic twitch contraction, the IC 50 value being 1.84 ± 0.23 μ m (n = 12). Unlike GABA, but like baclofen, 3‐aminopropylphosphinic acid did not produce an initial contraction. 3 The inhibitory effects of 3‐aminopropylphosphinic acid and baclofen in the guinea‐pig ileum were not significantly antagonized by bicuculline (10 μ m ), phentolamine plus propranolol (both 1 μ m ), yohimbine (1 μ m ), naloxone (1 μ m ), impromidine (1 μ m ) or 8‐phenyltheophylline (10 μ m ). The inhibitory effects of 3‐aminopropylphosphinic acid, but not of baclofen, were however antagonized by phaclofen (500 μ m ). In addition the effects of 3‐aminopropylphosphinic acid were abolished by baclofen desensitization in the guinea‐pig ileum. 4 3‐Aminopropylphosphinic acid, GABA and baclofen reduced the twitch contraction evoked by electrical field stimulation in the rat anococcygeus muscle. The IC 50 for 3‐aminopropylphosphinic acid inhibition of the anococcygeus contraction was 0.89 ± 0.15 μ m ( n = 8). 5 It is concluded that 3‐aminopropylphosphinic acid is a potent, selective GABA B agonist, being seven times more potent than baclofen in the guinea‐pig ileum and five times more potent than baclofen in the rat anococcygues muscle preparations.