Electrophysiological evidence that neurokinin A acts via NK-1 receptors in the cat dorsal horn.
The aim of the present study was to investigate the effects of the non-peptide NK-2 receptor antagonist, SR 48968 on the responses of dorsal horn neurons to iontophoretic application of the endogenous NK-2 receptor ligand, neurokinin A, and on synaptically elicited responses in chloralose-anaesthetized cats. The effect of iontophoretic application of neurokinin A was tested on 51 dorsal horn neurons. Of these, 43 were wide dynamic range and the rest non-nociceptive neurons. Neurokinin A induced a slow, prolonged excitation of 25 of the wide dynamic range neurons. All remaining neurons were unaffected. SR 48968 (50 microg to 1.0 mg/kg, i.v.) did not affect the on-going basal activity (n = 8) or the slow excitation induced by neurokinin A in any of the nine wide dynamic range neurons tested. To eliminate the possibility that systemically administered SR 48968 may not be reaching central sites, SR 48968 was also applied iontophoretically (70-120 nA) to five neurons and tested against excitatory responses to iontophoretically applied neurokinin A. The on-going activity of these cells were unaffected by SR 48968. The responses to neurokinin A were also unaffected suggesting that neurokinin A did not mediate its effects via NK-2 receptors. SR 48968 also had no effect on the excitatory responses of seven neurons to iontophoretic application of the NK-1 receptor agonist, substance P indicating that substance P actions are not mediated via NK-2 receptors and that SR 48968 did not react with NK-1 receptors. Responses of the neurons to non-noxious (hair) stimulation (n = 10), noxious mechanical (n = 5) and noxious thermal (n = 8) stimulation of the receptive field were also unaffected by SR 48968, suggesting a lack of participation of NK-2 receptors in these responses. However, responses of wide dynamic range neurons to neurokinin A were totally blocked by i.v. administration (0.5 mg/kg) of the NK-1 receptor antagonists CP-96,345 (n = 7) and CP-99,994 (n = 5) but not by CP-96,344 (n = 4), the inactive enantiomer of CP-96,345. These data suggest that neurokinin A, like substance P may be acting via NK-1, rather than NK-2 receptors, to produce excitation of wide dynamic range neurons in the dorsal horn of the cat spinal cord.
Radhakrishnan
V
V
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Henry
J L
JL
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002415:Cats; D007478:Iontophoresis; D015288:Neurokinin A / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects*; D013237:Stereoisomerism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects
D001549:Benzamides; D001713:Biphenyl Compounds; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; C066892:CP 96345