Comparison of the effects of substance P, neurokinin A, physalaemin and eledoisin in facilitating a nociceptive reflex in the rat.
The postulated existence of different types of tachykinin receptor in the spinal cord provided the basis for the present study; substance P, neurokinin A, eledoisin and physalaemin were administered intrathecally in the awake, restrained rat to compare their effects on reaction time in the tail-flick test. Each peptide was delivered via a chronically implanted subdural catheter to the lower lumbar vertebral level of the spinal cord. Intrathecal administration of 10 micrograms of substance P (6.5 nmol), eledoisin (8.0 nmol) or physalaemin (7.9 nmol) decreased the reaction time, respectively, to 22.5, 24.3 and 20.8% of the mean preadministration control values at 1 min after injection; similar administration of 6.5 nmol of neurokinin A produced a smaller decrease in reaction time, to only 49.5% of preadministration values. These effects were transient, the reaction times returning to preadministration values within 5 min. Each peptide also produced an initial vocalization followed by increased restlessness. Analysis of the dose-response curves indicated that the rank order of potency of the fitted curves for these peptides was physalaemin greater than or equal to substance P greater than or equal to eledoisin greater than neurokinin A. The results suggest that the receptor involved in facilitation of the tail-flick reflex resembles a substance P receptor rather than a receptor for one of the other endogenous neurokinins and that this receptor may bear some resemblance to the SP-P type postulated to exist in peripheral tissues.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004600:Eledoisin / Q000494:pharmacology; D007278:Injections, Spinal; D007705:Kinins / Q000494:pharmacology*; D008297:Male; D015288:Neurokinin A; D009479:Neuropeptides / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010803:Physalaemin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*
D007705:Kinins; D009479:Neuropeptides; D010803:Physalaemin; D013373:Substance P; D004600:Eledoisin; D015288:Neurokinin A