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

Abstract

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 Mg 2+, L-glutamate (3–100 μM) 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 μM) and Mg 2+ (600 μM). Preincubation with ethanol (30–100 mM) for 2 min inhibited contractions to L-glutamate by up to 50% and caused additive inhibition with 100 μM Mg 2+. Ethanol (65 mM) inhibition of L-glutamate (60 μM) contractions increaed from 30% after 2 min preincubation to a maximum of 60% following 10 min. Ethanol (65 mM) inhibited contractions induced by acetylcholine (0.1 μM), 5-hydroxytryptamine (0.16μM) or histamine (0.3 μM), 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 ethabol (10–300 mM), occuring immediately after addition to the longitudinal muscle myenteric plexus preparation, was still present in Mg 2+ deficient buffer. It was not blocked consistently by either APV (100 μM) or Mg 2+ (600 μM) suggesting that ethanol-induced contractions were not mediated via NMDA type receptors. These results suggest that ethanol selectively inhibits peripheral NMDA type excitatory amino acid receptors in addition to those in the CNS.