In vivo effects of the NMDA receptor agonist tetrazolyl-glycine related to the function of small-diameter primary afferents.
The NMDA receptor agonist tetrazolyl-glycine (TG; 100 microg kg(-1), i.v.) caused a depressor reflex in anaesthetized rats. The NMDA receptor antagonist MK-801 (300 microg kg(-1), i.v.) inhibited this depressor reflex, but not that induced by pentylenetetrazol (PTZ; 100 mg kg(-1), i.v.), indicating a selective effect of TG on NMDA receptors in vivo. Capsaicin pretreatment, which excludes the function of small-diameter primary afferent fibres, caused only a reduction of the TG-induced depressor reflex, suggesting a reduction of NMDA receptors. The absence of effects of TG and PTZ on the blood pressure in pithed rats excluded any peripheral vascular actions of TG and PTZ. The depressor reflex evoked by afferent nerve stimulation was also inhibited by MK-801 (300 microg kg(-1), i.v.), but not by the tachykinin antagonist L-742694 (10 mg kg(-1), i.v.), confirming the essential role of glutamate in the neurotransmission of signals at central terminals of small-diameter afferent neurons. Plasma protein extravasation in the rat hind paw, induced by neurotransmitters released at peripheral terminals of small diameter afferent neurons by antidromic nerve stimulation, was not influenced by MK-801, indicating that glutamate is either not released or has no effect there. It is concluded that the NMDA agonist TG is a valuable tool to study the functions of primary afferents in vivo.
Lembeck
F
F
Department of Experimental and Clinical Pharmacology, Graz, Austria.
Sieler
D
D
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D003655:Decerebrate State; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012584:Sciatic Nerve / Q000502:physiology; D012867:Skin / Q000098:blood supply; D013777:Tetrazoles / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C073649:(tetrazol-5-yl)glycine; D009020:Morphine; D002211:Capsaicin; D005998:Glycine