Use of NK(1) knockout mice to analyze substance P-induced edema formation.

Abstract

The mechanisms involved in tachykinin-induced neurokinin-1 (NK(1)) receptor-mediated edema formation have been studied in anesthetized wild-type and NK(1) knockout mice. Intradermally injected substance P (30-300 pmol), NK(1) agonists septide (3-30 pmol) and GR-73632 (3-30 pmol), and the mast cell-degranulating agent, compound 48/80 induced dose-dependent edema in wild-type skin, measured by the accumulation of intravenously injected (125)I-labeled albumin. Septide was 3-10x more potent than substance P. The tachykinins were inactive in knockout mice, but compound 48/80 induced a significantly greater edema (P < 0.05) than that observed in paired wild-type mice. Capsaicin (which releases endogenous neuropeptides) and exogenous tachykinins induced edema formation, which was reduced by the mast cell amine histamine H(1) antagonist mepyramine (P < 0.05). These findings confirm that tachykinins mediate edema formation via the NK(1) receptor and provide direct evidence that the septide-sensitive binding site is on the NK(1) receptor. Furthermore, results suggest that edema induced by the tachykinins, although totally dependent on NK(1) receptor-mediated mechanism, contains a mast cell-dependent component. The evidence is in keeping with an NK(1) receptor on mast cells.

• Authors: T Cao, N P Gerard, S D Brain
• Journal: The American journal of physiology (Am J Physiol) Vol. 277 Issue 2 Pg. R476-81 (08 1999) ISSN: 0002-9513 [Print] United States
• PMID: 10444554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histamine H1 Antagonists
• Receptors, Neurokinin-1
• Tachykinins
• Substance P
• p-Methoxy-N-methylphenethylamine
• Pyrilamine
• Capsaicin

Topics

• Animals
• Capsaicin (administration & dosage)
• Dose-Response Relationship, Drug
• Edema (chemically induced, drug therapy)
• Female
• Histamine H1 Antagonists (therapeutic use)
• Injections, Intradermal
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout (genetics)
• Pyrilamine (therapeutic use)
• Receptors, Neurokinin-1 (agonists, genetics, physiology)
• Skin Diseases (chemically induced, drug therapy)
• Substance P (administration & dosage)
• Tachykinins (administration & dosage)
• p-Methoxy-N-methylphenethylamine (administration & dosage)