Article date: June 1996
By: Yiu Wa Kwan, Man‐Piu Ngan, Kay‐Yan Tsang, Ha‐Man Lee, Lai‐Ah Chu, in Volume 118, Issue 3, pages 755-761
The modulatory effects of L‐glutamate and its structural analogues, and of γ‐aminobutyric acid (GABA), on sympathetic co‐transmission were studied in the rat isolated vas deferens exposed to electrical field stimulation (EFS).
Application of exogenous L‐glutamate caused a concentration‐dependent (1 μm‐3 mM) inhibition of the rapid twitch component of the biphasic EFS contraction. However, L‐glutamate (1 μm‐3 mM) had a minimal effect on the phasic contraction induced by exogenous adenosine 5′‐triphosphate (ATP, 150 μm) and noradrenaline (50 μm). Unlike L‐glutamate, D‐glutamate had no effect on the EFS contraction.
The L‐glutamate‐induced inhibition of the EFS contractions was significantly attenuated by the glutamate decarboxylase (GAD) inhibitor 3‐mercapto‐propionic acid (150 μm) and was abolished in the presence of the GABA transaminase (GABA‐T) inhibitor, 2‐aminoethyl hydrogen sulphate (500 μm).
The L‐glutamate‐induced inhibition of the electrically evoked contraction was not affected by the adenosine A1‐receptor antagonist, 8‐cyclopentyl‐1, 3‐dipropylxanthine (DPCPX)(30 nM), reactive blue 2 (30 μm) or the GABAA receptor antagonist bicuculline (50 μm). However, the GABAB receptor antagonist 2‐hydroxysaclofen (50 μm) significantly inhibited the L‐glutamate effect.
Similar to L‐glutamate, GABA also caused a concentration‐dependent (0.1 – 100 μm) inhibition of the EFS contractions. This GABA‐induced inhibition was not affected by either the GABAA receptor antagonist bicuculline (50 μm) or reactive blue 2 (30 μm). However, a significant attenuation of the GABA‐mediated effect was recorded with the GABAB receptor antagonist 2‐hydroxysaclofen (50 μm). Contractions of the vas deferens induced by exogenous ATP and noradrenaline were not affected by GABA (0.1 – 100 μm).
The L‐glutamate analogues, N‐methyl‐D‐aspartate (NMDA) (1 μm‐1 mM) and quisqualate (Quis 0.1 μm‐0.3 mM) had no effect, whilst kainate (Kain, 1 μm‐1 mM) caused an inhibition of the EFS‐induced contractions. Effects of Kain could be abolished by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dioxine (CNQX, 10 μm). NMDA, Quis and Kain had no effect on the exogenous ATP‐ or noradrenaline‐induced contractions.
It is concluded that the excitatory amino acid L‐glutamate modulates the electrically evoked vas deferens contraction through conversion to the inhibitory amino acid GABA by a specific GABA transaminase. The GABA formed may then act on GABAB receptors and cause inhibition of the contraction through a presynaptic mechanism.
The modulatory effects of L‐glutamate and its structural analogues, and of γ‐aminobutyric acid (GABA), on sympathetic co‐transmission were studied in the rat isolated vas deferens exposed to electrical field stimulation (EFS).
Application of exogenous L‐glutamate caused a concentration‐dependent (1 μm‐3 mM) inhibition of the rapid twitch component of the biphasic EFS contraction. However, L‐glutamate (1 μm‐3 mM) had a minimal effect on the phasic contraction induced by exogenous adenosine 5′‐triphosphate (ATP, 150 μm) and noradrenaline (50 μm). Unlike L‐glutamate, D‐glutamate had no effect on the EFS contraction.
The L‐glutamate‐induced inhibition of the EFS contractions was significantly attenuated by the glutamate decarboxylase (GAD) inhibitor 3‐mercapto‐propionic acid (150 μm) and was abolished in the presence of the GABA transaminase (GABA‐T) inhibitor, 2‐aminoethyl hydrogen sulphate (500 μm).
The L‐glutamate‐induced inhibition of the electrically evoked contraction was not affected by the adenosine A1‐receptor antagonist, 8‐cyclopentyl‐1, 3‐dipropylxanthine (DPCPX)(30 nM), reactive blue 2 (30 μm) or the GABAA receptor antagonist bicuculline (50 μm). However, the GABAB receptor antagonist 2‐hydroxysaclofen (50 μm) significantly inhibited the L‐glutamate effect.
Similar to L‐glutamate, GABA also caused a concentration‐dependent (0.1 – 100 μm) inhibition of the EFS contractions. This GABA‐induced inhibition was not affected by either the GABAA receptor antagonist bicuculline (50 μm) or reactive blue 2 (30 μm). However, a significant attenuation of the GABA‐mediated effect was recorded with the GABAB receptor antagonist 2‐hydroxysaclofen (50 μm). Contractions of the vas deferens induced by exogenous ATP and noradrenaline were not affected by GABA (0.1 – 100 μm).
The L‐glutamate analogues, N‐methyl‐D‐aspartate (NMDA) (1 μm‐1 mM) and quisqualate (Quis 0.1 μm‐0.3 mM) had no effect, whilst kainate (Kain, 1 μm‐1 mM) caused an inhibition of the EFS‐induced contractions. Effects of Kain could be abolished by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dioxine (CNQX, 10 μm). NMDA, Quis and Kain had no effect on the exogenous ATP‐ or noradrenaline‐induced contractions.
It is concluded that the excitatory amino acid L‐glutamate modulates the electrically evoked vas deferens contraction through conversion to the inhibitory amino acid GABA by a specific GABA transaminase. The GABA formed may then act on GABAB receptors and cause inhibition of the contraction through a presynaptic mechanism.
DOI: 10.1111/j.1476-5381.1996.tb15464.x
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