1 The modulatory effects of L-glutamate and its structural analogues, and of y-aminobutyric acid (GABA), on sympathetic co-transmission were studied in the rat isolated vas deferens exposed to electrical field stimulation (EFS). 2 Application of exogenous L-glutamate caused a concentration-dependent (1 /M -3 mM) inhibition of the rapid twitch component of the biphasic EFS contraction. However, L-glutamate (1 MM-3 mM) had a minimal effect on the phasic contraction induced by exogenous adenosine 5'-triphosphate (ATP, 150 MM) and noradrenaline (50 Mm). Unlike L-glutamate, D-glutamate had no effect on the EFS contraction. 3 The L-glutamate-induced inhibition of the EFS contractions was significantly attenuated by the glutamate decarboxylase (GAD) inhibitor 3-mercapto-propionic acid (150 Mm) and was abolished in the presence of the GABA transaminase (GABA-T) inhibitor, 2-aminoethyl hydrogen sulphate (500 gM).4 The L-glutamate-induced inhibition of the electrically evoked contraction was not affected by the adenosine Al-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)(30 nM), reactive blue 2 (30 Mm) or the GABAA receptor antagonist bicuculline (50 gM). However, the GABAB receptor antagonist 2-hydroxysaclofen (50 uM) significantly inhibited the L-glutamate effect. 5 Similar to L-glutamate, GABA also caused a concentration-dependent (0.1 -100 Mm) inhibition of the EFS contractions. This GABA-induced inhibition was not affected by either the GABAA receptor antagonist bicuculline (50 gM) or reactive blue 2 (30 gM). However, a significant attenuation of the GABA-mediated effect was recorded with the GABAB receptor antagonist 2-hydroxysaclofen (50 gM).Contractions of the vas deferens induced by exogenous ATP and noradrenaline were not affected by GABA (0.1-100 gM).6 The L-glutamate analogues, N-methyl-D-aspartate (NMDA) (1 MM-I mM) and quisqualate (Quis 0.1 Mm -0.3 mM) had no effect, whilst kainate (Kain, 1 MM-I mM) caused an inhibition of the EFSinduced contractions. Effects of Kain could be abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dioxine (CNQX, 10 gM). NMDA, Quis and Kain had no effect on the exogenous ATP-or noradrenaline-induced contractions. 7 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.
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