EFFECTS OF L-GLUTAMATE ON THE RESPONSES TO NERVE-STIMULATION IN RAT ISOLATED ATRIA

In rat atria isolated with their sympathetic fibres the chronotropic r esponses to nerve stimulation with pulses of 2 ms duration were reduce d in a concentration-dependent manner by 10 mu M to 1 mM L-glutamate ( Glu) and by 0.01 to 1.00 mu M (R,S)-3-hydroxy-5-methoxyloxasole-4-prop ionic acid (AMPA), whereas they were unaffected by other agonists of G lu receptors such as 1 mu M to 1 mM N-methyl-D-aspartic acid (NMDA), 1 0 mu M to 1 mM kainate and 1 to 100 mu M(F)-2-amino-4-phosphonobutyric acid (AP4). The reductions in the atrial responses to nerve stimulati on caused by Glu were not accompanied by alterations in either the bas al efflux of [H-3]noradrenaline or its overflow in response to the sti mulation. The sensitivity of the atria to exogenous noradrenaline was not modified by either Glu or AMPA. The decreases in the chronotropic responses caused by Glu and by AMPA were prevented by both the non-sel ective Glu receptor antagonist, 100 mu M kynurenic acid, and the selec tive AMPA receptor antagonist, 10 to 50 mu M 6,7-dinitroquinoxaline-2, 3-dione (DNQX). In addition, the adenosine receptor antagonist, 8-phen yltheophylline (10 mu M), as well as the muscarinic acetylcholine rece ptor antagonist, atropine (3 mu M), prevented the inhibitory effects o f both Glu and AMPA on the chronotropic responses of rat isolated atri a. Since both adenosine and acetylcholine are known to exert negative inotropic and chronotropic effects in cardiac tissues, it is proposed that Glu could contribute, through the interaction with receptors of t he AMPA type, to facilitate the release of adenosine and acetylcholine from the atria. The latter substances, in turn, could decrease the at rial rate. The location of the AMPA receptors in the rat heart as well as the sites where either acetylcholine or adenosine might act to exe rt their actions cannot be elucidated from the present results.