title: NMDA receptors and associated signaling pathways: a role in knee joint blood flow regulation.
abstract: Blood flow changes in response to N-methyl-D-aspartate (NMDA) receptor activation were assessed using a laser Doppler flowmeter. Treatment of the joint with NMDA (1 mM; 0.1 ml) resulted in a significant increase in blood flow while the control phosphate buffer (PB) injection (0.1 M; pH 7.4) had no effect. Blocking NMDA receptors with the antagonist MK 801 (0.1 mM) prevented the increase in blood flow observed following NMDA injection, suggesting specificity of action. The NMDA-evoked vasodilation has been shown to be mediated through activation of several intracellular signaling transduction molecules, namely nitric oxide, release of calcitonin gene-related peptide (CGRP) and CAM kinase II. Blocking actions of these molecules with L-NAME (10 mg/ml), CGRP(8-37) (0.01 mM) and KN-93 (1 microM), respectively, prevented the increase in blood flow induced by NMDA in the present study. These results provide new evidence implicating NMDA receptors in knee joint inflammatory responses.
authors.affiliation: Department of Anatomy and Neuroscience, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
authors.forename: Nada B
authors.initials: NB
authors.lastname: Lawand
authors.forename: William J
authors.initials: WJ
authors.lastname: Reddig
authors.forename: Alice E
authors.initials: AE
authors.lastname: Cashin
authors.forename: Karin N
authors.initials: KN
authors.lastname: Westlund
authors.forename: William D
authors.initials: WD
authors.lastname: Willis
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007719:Knee Joint / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D015740:Calcitonin Gene-Related Peptide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016291:Dizocilpine Maleate; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D016202:N-Methylaspartate; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; C058636:calcitonin gene-related peptide (8-37); C072105:KN 93; D000096926:Benzenesulfonamides; C080122:7-nitroindazole