Effects Of Exogenous Glutamate Research Articles

Effects of Exogenous Glutamate and Kainate on Electric Field-stimulated Contractions of Isolated Human Ureter

A neurotransmitter role for glutamate in the autonomous nervous system was recently demonstrated in the gastrointestinal tract, and its stimulatory effect on spontaneous motility of human ureter was shown. The aim of our study was to investigate the effects of glutamate on the release of neurotransmitters from intramural nerves of the human ureter. The effects of exogenous glutamate were tested on electric field-stimulated contractions of isolated human ureter, taken from 16 adult patients after nephrectomy. The longitudinal tension and intraluminal pressure of the isolated ureter were recorded simultaneously. The electric field stimulation was done with square wave pulses (20 V through electrodes, 400 mA, duration 1 ms, frequency 16 Hz). The pulse trains lasted for 30 s, a with 30-s pause. Glutamate (7.9 x 10(-6) M/L to 10.6 x 10(-3) M/L) and kainic acid (6.3 x 10(-8) M/L to 2.2 x 10(-5) M/L) produced a concentration-dependent decrease in the electric field-stimulated activity of the isolated preparations. However, N-methyl-D-aspartic acid (9.1 x 10(-8) M/L to 3.1 x 10(-5) M/L), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (7.2 x 10(-8) M/L to 3.2 x 10(-6) M/L) and (+/-)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid (7.7 x 10(-8) M/L to 6.5 x 10(-5) M/L) were ineffective. The electric field-stimulated contractions of isolated ureter were also inhibited by lidocaine (3.70 x 10(-4)M/L) and atropine (1.00 x 10(-6)M/L). The results of our study suggest that glutamate inhibits electric field-stimulated release of acetylcholine in the human ureter through activation of kainate ionotropic receptors, located on the intramural nerve fibers.

Excitatory amino acid receptors and transmitter release in the retina

The effects of excitatory amino acids and some analogues on the release of GABA and ACh from amacrine cells were studied. The release of endogenous GABA from the isolated rat retina was measured by HPLC. When animals were pretreated with γ-vinyl-GABA (GVG), glutamate evoked a large efflux of GABA but kainate, quisqualate and N- methyl- d-aspartate ( NMDA) were relatively ineffective. The glutamate evoked release of GABA was calcium dependent and was blocked by the antagonist, piperidine-dicarboxylic acid (PDA) indicating that activation of excitatory amino acid receptors was involved in the response. The release of [ 3H]ACh from the rabbit retina was strikingly increased by homocysteate and this effect was blocked by NMDA. Since NMDA also blocked the light evoked release of [ 3H]ACh but not the effects of exogenous glutamate or aspartate, it is possible that homocysteate may be a bipolar cell transmitter released onto cholinergic amacrine cells.

Effects of glutamic acid on cardiac function and energy metabolism of rat heart during ischaemia and reperfusion

The effects of exogenous glutamate (20 m m) on myocardial energy metabolism and cardiac function during low-flow ischaemia and subsequent reperfusion were studied in isolated working rat hearts. Hearts were made severely ischaemic for 60 min by reducing the perfusion rate to 0.17 ml/min, and then reperfused for 30 min. Low-flow ischaemia resulted in a 50% reduction of myocardial ATP, a 70% reduction of both creatine phosphate (CP) and GTP, and a 250% rise in AMP. After reperfusion, CP was restored to normal levels but ATP and GTP remained significantly low. All hearts failed completely to recover cardiac pump function. The addition of glutamate to the perfusate during low-flow ischaemia had no significant effect on myocardial highenergy phosphates (HEP) but slightly increased succinate production. Subsequent reperfusion without added glutamate resulted in the recovery of 62% of pre-ischaemic aortic flow rate, as well as restoration of myocardial ATP and GTP to 70% of their control values and of creatine phosphate to supranormal levels. Reperfusion with added glutamate did not raise HEP levels any further but did increase recovery of cardiac function to 92% or more of pre-ischaemic values. Thus, by mechanism(s) which are not yet clear but which may include an increase in HEP via anaerobic succinate production, elevated levels of exogenous glutamate exert a highly beneficial effect on the post-ischaemic recovery of cardiac function.