Interaction of ethanol and L-glutamate in the guinea pig ileum myenteric plexus

The guinea pig ileum longitudinal muscle myenteric plexus has recently been shown to contain receptors for excitatory amino acids like L-glutamate which are pharmacologically similar to the N-methyl-D-aspartate (NMDA) receptor subtype in the central nervous system (CNS). The present study utilized the longitudinal muscle myenteric plexus preparation to determine whether the reported ability of acute ethanol treatment to inhibit NMDA receptor activation in mammalian CNS preparations also occurs in the periphery. In the absence of Mg2+, L-glutamate (3-100 microM) induced transient contractions in longitudinal muscle myenteric plexus that could be blocked by atropine. Contractile responses to L-glutamate were completely blocked by D,L-2-amino-5-phosphonovalerate (APV; 100 microM) and Mg2+ (600 microM). Preincubation with ethanol (30-100 mM) for 2 min inhibited contractions to L-glutamate by up to 50% and caused additive inhibition with 100 microM Mg2+. Ethanol (65 mM) inhibition of L-glutamate (60 microM) contractions increased from 30% after a 2 min preincubation to a maximum of 60% following 10 min. Ethanol (65 mM) inhibited contractions induced by acetylcholine (0.1 microM), 5-hydroxytryptamine (0.1 microM) or histamine (0.3 microM), by no more than 10% suggesting that impairment of smooth muscle or cholinergic neuronal activity were not likely responsible for the 40% inhibition of L-glutamate contractions seen with ethanol. A previously identified contractile response to ethanol (10-300 mM), occurring immediately after addition to the longitudinal muscle myenteric plexus preparation, was still present in Mg2+ deficient buffer.(ABSTRACT TRUNCATED AT 250 WORDS)