MORPHINE AND NALOXONE ACT SIMILARLY ON GLUTAMATE-CAUSED GUINEA-PIG ILEUM CONTRACTION

Abstract

Both morphine (M) and naloxone (NL) have been reported to have NMDA receptor blocking effects, regarded as the reason of opiate physical dependence development. On the other hand, glutamate (GLU) has been known to induce the contraction of isolated guinea pig ileum via acetylcholine release. Therefore, different concentrations of M or NL were investigated on the 1 mM GLU-induced contraction of isolated guinea pig ileum fixed at a resting tension of 1 g in isolated organ bath. The mean value (359.3 +/- 20 mg) of the GLU-elicited contraction force was significantly reduced (318.4 +/- 19.4) by 25 nM M concentration in the medium. Consequently, 500 and 750 nM M caused further decreases in a rather dose-dependent manner (270.8 +/- 17.4 and 167.8 +/- 16.5 mg, respectively). One micromolar M contraction nearly abolished (8.0 +/- 8.2 mg) the GLU-induced contraction. A similar effect was obtained with the naloxone concentrations of 10, 20, 40, and 50 muM. In addition, NL has been shown to elicit the contraction of the isolated M-dependent guinea pig ileum. In the present study, 20- and 30-muM NL concentrations in the bathing medium caused the contraction of the ileum made M-dependent by preincubation with M (333.0 +/- 32.4 and 309.5 +/- 17.7 mg, respectively). These contraction forces were significantly reduced when the NL concentration was increased to 40 muM. And, 50 muM NL concentration not only failed to induce contraction but caused a relaxation (- 10.6 +/- 2.3) as well. The results were considered supporting evidence for the fact that both M and NL are NMDA receptor blockers. While the affinity of NL for NMDA receptors is much higher than that of M, the blocking effect is much weaker than that of M. For this reason, NL precipitates abstinence syndrome in opiate-dependent mammals by displaying opiate from receptors without preventing them from having much stronger stimulation of aspartate and GLU than normal.