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Antagonism of GABA B ‐receptor‐mediated responses in the guinea‐pig isolated ileum and vas deferens by phosphono‐analogues of GABA
Author(s) -
Kerr David I.B.,
Ong Jennifer,
Prager Rolf H.
Publication year - 1990
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.1476-5381.1990.tb14719.x
Subject(s) - vas deferens , antagonism , ileum , guinea pig , pharmacology , receptor , endocrinology , biology , medicine , chemistry
1 The phosphono‐analogues of γ‐aminobutyric acid (GABA), 4‐amino‐butylphosphonic acid (4‐ABPA), 3‐amino‐2‐(4‐chlorophenyl)‐propylphosphonic acid (phaclofen) and 3‐amino‐2‐cyclohexylpropylphosphonic acid, each antagonized the GABA‐ and baclofen‐induced GABA B ‐receptor‐mediated depression of twitch responses to transmural stimulation in the guinea‐pig isolated ileum, in a concentration‐dependent, reversible and surmountable manner (apparent pA 2 = 4.0 ± 0.1, 4 ± 0.2 and 3.7 ± 0.2 respectively, compared with 3.9 ±0.1 for δ‐aminovaleric acid). No such activity was found in a variety of related analogues. 2 By contrast, 3‐amino‐propylphosphonic acid (3‐APPA) behaved as a partial agonist, itself partly depressing ileal twitch contractions in a manner sensitive to 4‐ABPA and phaclofen, as well as antagonizing the depression of the ileal twitch by GABA and baclofen (apparent pA 2 = 4.0 ± 0.2). 3 Both 4‐ABPA and phaclofen also antagonized the baclofen‐induced depression of the twitch in the guinea‐pig isolated vas deferens (apparent pA 2 = 4.0 ± 0.1 for each), whilst 3‐APPA behaved as a partial agonist, slightly depressing the vas twitch, and antagonised the baclofen‐induced depression of the twitch (apparent pA 2 = 3.9 ±0.1). 4 None of these phosphono‐analogues exhibited any action at ileal GABA A ‐receptors, nor influenced the ileal twitch depression with morphine, adenosine or noradrenaline, suggesting their selectivity as antagonists at GABA B ‐receptors.