Abstract
γ-Vinyl GABA (vigabatrin; VGB), an irreversible inhibitor of GABA-transaminase, was evaluated for its effect on the contractile responses to PGE
2 or its precursor arachidonic acid (AA) in guinea pig ileum (GPI) and non-pregnant rat uterus. Rationale behind this study was the rise in γ-aminobutyric acid (GABA) contents in the peripheral organs after treatment with GABAergic agents and extensive interconnections of neuromediators and their interactions.
Indomethacin, the standard NSAID, at 6.1×10
−5 and 12.2×10
−5
M concentrations highly significantly (
P<0.001) inhibited contractile responses induced by AA (4.3×10
−5
M) in the isolated GPI. Incubation of the GPI segments with VGB at different concentrations (25, 100 and 200
mM) failed to inhibit AA-induced contractile responses in the same preparation. In fact, VGB at 25
mM significantly (
P<0.05) potentiated the contractile effect of AA 4.3×10
−5
M. Incubation of the same tissue with GABA at 13×10
−3 and 26×10
−3
M inhibited responses elicited by AA at 4.3×10
−5
M that was significant (
P<0.05) only with low concentration of GABA. Conversely, a higher concentration (64×10
−3
M) of GABA was needed to antagonise PGE
2 (9.4×10
−6
M)-induced contractions in the same tissue. Almost similar results (i.e. inhibition of contractile responses to AA and PGE
2) were obtained with isolated non-pregnant rat uterus. These findings suggested that GABA had the potential to inhibit prostaglandin (PG) synthesis and/or antagonise PGE
2 responses in isolated GPI and rat uterus.
The addition of 35 or 70
μl of rat aorta incubation medium caused a dose-dependent inhibition of ADP-induced aggregation being 21.5 and 43.5%, respectively, an indication of prostacycline (PGI
2) contents. Pre-incubation of rat aortic tissues with VGB (96.8
mM) significantly (
P<0.05) reversed the anti-aggregatory activity of control aortic prostacycline on ADP-induced aggregation. These findings suggested that VGB might inhibit PGI
2 activity through the inhibition of its synthesis.