Stimulation of peripheral cholinergic nerves by glutamate indicates a new peripheral glutamate receptor

The bronchial smooth muscle of the rat was examined for contractile responses to excitatory amino acids. The nerve-mediated contraction induced by electrical field stimulation was enhanced by exogenous L-glutamate (L-Glu). The apparent affinity (ED50) of L-Glu was 3.5 +/- 0.1 mM. Both tetrodotoxin and hemicholinium-3 completely abolished the electrical field-induced contraction and therefore the potentiation by L-Glu, which indicates that L-Glu has a prejunctional effect. Concentrations of L-Glu higher than 22 mM inhibited the electrical field-induced contractions and enhanced the tonus of the smooth muscle by postjunctional stimulation. The ED50 of exogenous ACh was not altered by L-Glu. High concentrations (62 mM) of L-Glu increased the intrinsic activity (alpha) of ACh, indicating a postjunctional potentiation of ACh-induced contractions. L-Glu did not inhibit the activity of acetylcholinesterase, therefore the postjunctional potentiation was not due to ACh accumulation. Inhibition of the electrical field-induced contraction was seen with high concentrations of D-Glu, L-aspartate (L-Asp), L-alpha-amino adipate and ibotenate. Neither glutamate diethyl ester nor 2-amino-5-phosphonovalerate had any inhibitory effects on the L-Glu- and L-Asp-induced alterations of the electrical field-stimulated contraction or on the L-Glu-enhanced tonus of the bronchial smooth muscle. Kainate, N-methyl-D-aspartate, quisqualate and N-acetyl-aspartyl-glutamate had only minor transient potentiating effects on the electrical field-induced contraction. The results provide evidence for a L-Glu receptor in rat bronchi that has a different specificity for glutamate agonists and antagonists than the L-Glu receptor described in the CNS. The receptor seems to be located prejunctionally and enhances nerve-mediated responses and thereby stimulates the bronchial smooth muscle to contract. The possible involvement of this type of receptor in the 'Chinese restaurant syndrome' is discussed.