Amino acids as modulators of cholinergic nerves in airways

The bronchial smooth muscle of rat was examined for contractile responses to excitatory amino acids. The electrical field stimulation (EFS) which induces release of ACh, induced contraction which was enhanced by exogenous L-glutamate (L-glu). The ED50 of L-glu was 3.5 +/- 0.1 mM. Inhibition of the release by TTX or by HC-3 completely abolished the potentiation of the EFS-induced contraction by L-glu. The effect of L-glu is therefore probably a prejunctional effect. Concentrations of L-glu higher than 22 mM inhibited the EFS evoked contractions, and enhanced the tonus of the muscle by a postjunctional stimulation. The ED50 of ACh was not altered by L-glu. In contrast, an increase of the intrinsic activity (alpha) of ACh was seen, providing evidence for a postjunctional potentiation of ACh induced contraction. L-glu did not inhibit AChE-activity at concentrations up to 50 mM, indicating that the effect is not due to an accumulation of ACh. A relaxation of the EFS-induced bronchial smooth muscle contraction was seen with high concentrations of D-glu, L-asp, L-alpha-amino adipate and ibotenate. Neither L-GDEE nor DL-APV had any inhibitory effect on L-glu and L-asp induced alteration of EFS-evoked contraction or on the L-glu enhanced tonus of the bronchial smooth muscle. Kainate, NMDA and quisqualate had only minor transient potentiating effects on the EFS-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)