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Antagonism of GABAB-receptor-mediated responses in the guinea-pig isolated ileum and vas deferens by phosphono-analogues of GABA.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 1990 Feb; Vol. 99 (2), pp. 422-6. - Publication Year :
- 1990
-
Abstract
- 1. The phosphono-analogues of gamma-aminobutyric acid (GABA), 4-amino-butylphosphonic acid (4-ABPA), 3-amino-2-(4-chlorophenyl)-propylphosphonic acid (phaclofen) and 3-amino-2-cyclohexylpropyl-phosphonic acid, each antagonized the GABA- and baclofen-induced GABAB-receptor-mediated depression of twitch responses to transmural stimulation in the guinea-pig isolated ileum, in a concentration-dependent, reversible and surmountable manner (apparent pA2 = 4.0 +/- 0.1, 4 +/- 0.2 and 3.7 +/- 0.2 respectively, compared with 3.9 +/- 0.1 for delta-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 pA2 = 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 pA2 = 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 pA2 = 3.9 +/- 0.1). 4. None of these phosphono-analogues exhibited any action at ileal GABAA-receptors, nor influenced the ileal twitch depression with morphine, adenosine or noradrenaline, suggesting their selectivity as antagonists at GABAB-receptors.
- Subjects :
- Adenosine pharmacology
Animals
Bicuculline pharmacology
Electric Stimulation
Female
Guinea Pigs
Ileum drug effects
In Vitro Techniques
Male
Morphine pharmacology
Norepinephrine pharmacology
Structure-Activity Relationship
Vas Deferens drug effects
Muscle, Smooth drug effects
Receptors, GABA-A drug effects
gamma-Aminobutyric Acid analogs & derivatives
gamma-Aminobutyric Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 99
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 2158379
- Full Text :
- https://doi.org/10.1111/j.1476-5381.1990.tb14719.x