Modulation of peripheral inflammation by the substance P N-terminal metabolite substance P1-7.

Abstract

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.

• Authors: Daniel Wiktelius, Zeinab Khalil, Fred Nyberg
• Journal: Peptides (Peptides) Vol. 27 Issue 6 Pg. 1490-7 (Jun 2006) ISSN: 0196-9781 [Print] United States
• PMID: 16414148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• Vasodilator Agents
• Substance P
• Naloxone

Topics

• Animals
• Central Nervous System (metabolism)
• Dose-Response Relationship, Drug
• Inflammation (metabolism)
• Male
• Naloxone (pharmacology)
• Neurons (pathology)
• Peptides (chemistry)
• Protein Structure, Tertiary
• Rats
• Rats, Sprague-Dawley
• Sciatic Nerve (injuries)
• Substance P (chemistry, metabolism)
• Vasodilator Agents (metabolism)