An analogue of growth hormone releasing factor (GRF), (Ac-Try1, D-Phe2)-GRF-(1-29), specifically antagonizes the facilitation of the flexor reflex induced by intrathecal vasoactive intestinal peptide in rat spinal cord.
The effect of intrathecal (i.t.) vasoactive intestinal peptide (VIP) and an analogue of growth hormone releasing factor (GRF) with putative VIP antagonistic property, (Ac-Try1, D-Phe2)-GRF-(1-29), on the nociceptive flexor reflex was studied in decerebrate, spinalized, unanesthetized rats. VIP (10 pM) facilitated the flexor reflex for several minutes. A similar facilitation was induced by the VIP antagonist applied i.t. with a potency 15 times less than that of VIP. Pre-administration of the VIP antagonist dose-dependently antagonized the reflex facilitation by i.t. VIP. In contrast, the reflex facilitation induced by i.t. substance P, somatostatin, calcitonin gene-related peptide and galanin was not influenced by the VIP-antagonist. The VIP antagonist by itself did not depress the flexor reflex over the dose range of 3 pM-3 nM and neither did it block the facilitation of the flexor reflex induced by a brief conditioning electrical stimulus train that activated the C-afferents in skin innervated by the sural nerve. The present results indicate that this GRF analogue is an effective and specific VIP antagonist in the rat spinal cord. Furthermore, it is suggested that VIP may not be involved in the transmission of cutaneous nociceptive information under normal conditions.
Xu
X J
XJ
Department of Clinical Physiology, Karolinska Institute, Huddinge, Sweden.
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D017337:Sermorelin / Q000031:analogs & derivatives; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013497:Sural Nerve / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone; C045616:somatotropin releasing hormone (1-29)-amide, N-Ac-Tyr(1)-Phe(2)-