Demonstration of a 'septide-sensitive' inflammatory response in rat skin

Area of Science:

• Pharmacology
• Neuroscience
• Dermatology

Background:

• Tachykinins, including substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), are implicated in inflammatory responses.
• The role of specific tachykinin receptor subtypes (NK1, NK2, NK3) in mediating plasma protein extravasation in rat skin requires further elucidation.

Purpose of the Study:

• To investigate the involvement of NK1, NK2, and NK3 receptors in mediating plasma protein extravasation induced by tachykinins in rat skin.
• To differentiate the mechanisms of action between SP and the synthetic hexapeptide septide in inducing oedema.

Main Methods:

• Intradermal administration of natural tachykinins and selective receptor agonists/antagonists in rat skin.
• Measurement of plasma protein extravasation (oedema) and assessment of the effects of nitric oxide (NO) synthase inhibition and mast cell degranulation.

Main Results:

• Selective NK1 receptor agonists ([Sar9]SP sulphone and septide) were more potent than SP in inducing plasma protein extravasation.
• NK2 and NK3 receptor agonists and antagonists did not significantly affect oedema formation.
• The NK1 receptor antagonist RP 67,580 differentially inhibited responses to septide and SP, suggesting distinct receptor interactions.
• Septide-induced oedema was nitric oxide (NO)-dependent and mast cell-independent, whereas SP-induced oedema was NO-independent.

Conclusions:

• These findings support the existence of a distinct 'septide-sensitive' receptor/binding site involved in tachykinin-induced oedema formation.
• The study highlights differing mechanisms of action for SP and septide in mediating plasma protein extravasation in rat skin, with implications for understanding neurogenic inflammation.