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.
Publication types
-
Comparative Study
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Benzylamines / pharmacology
-
Calcitonin Gene-Related Peptide / pharmacology
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
-
Dizocilpine Maleate / pharmacology
-
Enzyme Inhibitors / pharmacology
-
Excitatory Amino Acid Antagonists / pharmacology
-
Indazoles / pharmacology
-
Knee Joint / blood supply*
-
Knee Joint / drug effects
-
Male
-
N-Methylaspartate / pharmacology
-
NG-Nitroarginine Methyl Ester / pharmacology
-
Nitric Oxide Synthase / antagonists & inhibitors
-
Peptide Fragments / pharmacology
-
Protein Kinase Inhibitors / pharmacology
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
-
Receptors, N-Methyl-D-Aspartate / physiology*
-
Signal Transduction*
-
Sulfonamides / pharmacology
Substances
-
Benzylamines
-
Enzyme Inhibitors
-
Excitatory Amino Acid Antagonists
-
Indazoles
-
Peptide Fragments
-
Protein Kinase Inhibitors
-
Receptors, N-Methyl-D-Aspartate
-
Sulfonamides
-
calcitonin gene-related peptide (8-37)
-
KN 93
-
N-Methylaspartate
-
Dizocilpine Maleate
-
Nitric Oxide Synthase
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Calcitonin Gene-Related Peptide
-
7-nitroindazole
-
NG-Nitroarginine Methyl Ester