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 on gut smooth muscle strips have been demonstrated, the mechanisms, and particularly 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 microM, 150 microM, 20 microM, 33 microM, and 2.7 microM and 7.9 microM, respectively. L-SOP (0.1 microM-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 microM). The glutamate-evoked contractions were not affected by atropine, verapamil and nicardipine, blocked by CNQX (0.01 microM), or potentiated by Mg2+ (0.01-100 microM), ketamine (0.01-100 microM) and DL-AP5 (0.1-100 microM), as well as L-trans-2,4-PDC (1-100 microM). Analysis of glutamate's action on rat rectum (EC50 = 44 microM) could only be carried out at the early stages, as half of the preparations were not affected by glutamate. Only 5 out of 26 human 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 on 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 on 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.
Milovanovic
D R
DR
Department of Pharmacology, Medical Faculty, University of Kragujevac, Kragujevac, Serbia, Yugoslavia. piki@ptt.yu
Jankovic
S M
SM
D000368:Aged; D000818:Animals; D001224:Aspartic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D005748:Gastric Fundus / Q000737:chemistry / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007420:Intestine, Large / Q000187:drug effects / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D012007:Rectum / Q000737:chemistry / Q000187:drug effects; D013270:Stomach / Q000737:chemistry / Q000187:drug effects / Q000601:surgery
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D001224:Aspartic Acid; D018698:Glutamic Acid; D016318:Quisqualic Acid; D011392:Proline