Modulation of peripheral inflammation by the substance P N-terminal metabolite substance P1-7.
The N-terminal metabolite of the undecapeptide substance P (SP), substance P1-7 (SP1-7), is known to modulate nociception in the central nervous system (CNS) and often has opposite effects from SP. This study investigated the ability of SP(1-7) to modulate the vasodilatation response to SP in anaesthetized rats under different injury conditions using a blister model of inflammation on the hind footpad. The results indicated that SP1-7 inhibited the vascular response to SP in a dose-dependent manner. The putative antagonists naloxone and D-Pro2-D-Phe7-SP1-7 (D-SP1-7) reversed the effect of SP1-7. D-SP1-7 improved the responsiveness to SP under chronic nerve injury, which suggests a role for endogenous SP1-7 in this model. SP1-7 did not inhibit the response to electrical stimulation of the sciatic nerve, which indicates that the heptapeptide interacts at a post-terminal binding site. The current results suggest that SP1-7 may have inhibitory properties in inflammation, analogous to its antinociceptive role in the central nervous system.
Wiktelius
Daniel
D
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, P.O. Box 591, S-751 24 Uppsala, Sweden.
Khalil
Zeinab
Z
Nyberg
Fred
F
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D013373:Substance P / Q000737:chemistry / Q000378:metabolism*; D014665:Vasodilator Agents / Q000378:metabolism
D010455:Peptides; D014665:Vasodilator Agents; D013373:Substance P; D009270:Naloxone