Isolated porcine coronary arteries (PCA) contracted by depolarization with high K0 or by histamine (10 microM) were relaxed concentration-dependently by glutamic acid, aspartic acid, N-methyl-D-aspartate (NMDA) and, gamma-aminobutyric acid (GABA). In the PCA preparations contracted by high K0 or histamine the effects were monophasic, but the histamine-induced effects were more sustained and of larger amplitude. The ED50 values of cumulative concentration-response (CCR) curves obtained for the relaxation induced by L-glutamate in histamine-stimulated PCA preparations were shifted from 0.8 mM to 0.25 microM in presence of 1 mM glycine, a co-agonist required for the activation of NMDA receptors. The relaxations resulting from low-affinity binding of L-glutamic were dependent on Ca0 as evidenced by the shift of CCR curves to the right in the presence of 5-100 mM K0. In contrast, CCR curves obtained for contractions induced by NaF (1.5-12 mM), were significantly shifted to the left (from 6.3 to 3.1 mM). A depression of the maximum effect observed at higher F- concentrations was reversed by addition of 5 mM Mg0. Data show that glutamate induces a vasorelaxation that may be associated with symptoms seen in Chinese restaurant syndrome.