Simultaneous activation of N-methyl-D-aspartate and neurokinin-1 receptors modulates c-Fos and Zif/268 expression in the rat trigeminal nucleus caudalis.
We examined the acute expression of c-Fos or Zif/268 by simultaneous activation of N-methyl-D-aspartate receptor and neurokinin-1 receptor of the trigeminal nucleus caudalis in anesthetized rats. A selective N-methyl-D-aspartate receptor agonist, N-methyl-D-aspartate, and/or a selective neurokinin-1 receptor agonist, substance P, was applied topically to the dorsal surface of the spinal trigeminal tract. Immunohistochemically stained nuclei for c-Fos and Zif/268 at laminae I and II of the trigeminal nucleus caudalis were counted. Ipsilateral c-Fos and Zif/268 were increased significantly dose-dependently by N-methyl-D-aspartate (at 136 and 340 microM, and at 68, 136 and 340 microM, respectively). On the contralateral side, only Zif/268 increased significantly (at 68, 136 or 340 microM). These increases were abolished by D-2-amino-5-phosphonovaleric acid (at 25 mM), a selective N-methyl-D-aspartate receptor antagonist. Substance P (at 3.7 or 7. 4 microM) significantly increased dose-dependently ipsilateral c-Fos and Zif/268. On the contralateral side, only c-Fos was significantly increased (at 3.7 and 7.4 microM). These increases were abolished by D-2-amino-5-phosphonovaleric acid (at 25 mM) and L-703,606 (at 10 microM), a selective neurokinin-1 receptor antagonist. The combined application of N-methyl-D-aspartate 340 microM + substance P (at 0.74 or 3.7 microM) significantly increased ipsilateral c-Fos compared to either agent alone. Combined application of N-methyl-D-aspartate 340 microM + substance P at 0.74, 3.7 or 7.4 microM significantly increased ipsilateral Zif/268 expression compared to either drug alone. Other combinations did not increase c-Fos and Zif/268. Our results indicate that activation of N-methyl-D-aspartate or neurokinin-1 receptor of the trigeminal nucleus caudalis contributes to the acute induction of both c-Fos and Zif/268 on the ipsilateral superficial layer of this nucleus and simultaneous activation of both receptors by their agonists with specific concentrations produces a marked expression of these proteins. Simultaneous activation of N-methyl-D-aspartate and neurokinin-1 receptors under some specific conditions may augment synaptic transmission, contributing to long-term neuronal change.
Koganemaru
M
M
Department of Anesthesiology, Miyazaki Medical College, Miyazaki, Japan. miekokin@post1.miyazaki-med.ac.jp
Takasaki
M
M
Nishimori
T
T
D000818:Animals; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004268:DNA-Binding Proteins; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; D014157:Transcription Factors; D013373:Substance P; D016202:N-Methylaspartate