A pharmacological analysis of the contractile effects of glutamate on rat and human isolated gut smooth muscle strips

Although the contractile effects of glutamate and related excitatory amino acids oil gut smooth muscle strips have been (demonstrated, the mechanisms, and particular-A, the physiological importance of that action, remain unknown. In this study glutamate, aspartate, AMPA, quisqualate, cis-ACPD and (2R,4R)-APDC evoked concentration-dependent contraction of isolated adult rat gastric fundus, with EC50 values of 210 muM, 150 muM, 20 muM, 33 muM, 2.7 muM and 7.9 muM, respectively L-SOP (0.1 muM-1.9 mM) did not change the basal tone of the preparations. The maximal contractions evoked by glutamate (20 mM) were 38.83% compared with those elicited by acetylcholine (20 muM). The glutamate-evoked contractions were not affected by atropine, verapamil (aid nicardipine, blocked by, CNQX (0.01 muM), or potentiated by Mg2+ (0.01-100 muM), ketamine (0.01-/00 muM) and DL-AP5 (0.1-100 muM), as well as L-trans-2,4-PDC (1-100 muM). Analysis of glutamates action on rat rectum (EC50 = 44 muM) could only be carried out at the early stages, as half of the preparations were not affected by glutamate. Only 5 out of 26 bullion longitudinal and circular smooth muscle preparations taken from the stomach and three segments of the large intestine were very slightly contracted by glutamate, excluding further analysis. The contractile effects of glutamate Oil rat gut smooth muscles were mediated by multiple GluR (non-NMDA > NMDA > group I/II mGluRs) located primarily on smooth muscle cells but functional GluRs oil neurons and/or nerve fibers of myenteric nervous plexuses could not be excluded. To fully understand the physiological significance of glutamate-evoked contractions in the gut, more research is required, most likely using many different methodological approaches. (C) 2002 Prous Science. All rights reserved.