Study of the interaction of glutamatergic and nitrergic signalling in conditions of the experimental airways hyperreactivity.
BACKGROUND
Glutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We investigated the effect of agents modulating the activity of these systems on the experimental ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled nitric oxide (eNO) levels.


METHODS
We used the agonists of NMDA receptors - N-methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective competitive antagonist (DL-2-amino-5-phosphonovaleric acid - AP-5) and selective non-competitive antagonist (dizocilpine - MK-801) of these receptors. We used also non-specific inhibitor of NO synthases N(ω)-nitro-L-arginine methyl ester (L-NAME). The airways responsiveness to histamine or acetylcholine was evaluated under in vitro conditions.


RESULTS
NMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle. We recorded the changes in eNO levels. The activation of NMDA receptor with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME caused the fall of eNO levels. MK-801 shows (within the group) the more expressive effect in the eNO levels during sensitization than AP-5 group.


CONCLUSIONS
The results confirm the possibility of NMDA receptors participation in the experimental airways hyperreactivity.
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
Martina
M
Antošová
Anna
A
Strapková
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism* / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016202:N-Methylaspartate / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D012970:Sodium Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D018683:Excitatory Amino Acid Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D006632:Histamine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D012970:Sodium Glutamate