Several mediators appear to interact in neurogenic inflammation

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Plasma protein extravasation is a key component of neurogenic inflammation.
• Substance P (SP) is a known mediator, but other tachykinins and neuropeptides role require further investigation.

Purpose of the Study:

• To investigate the role of novel mammalian tachykinins (neurokinin A [NKA] and neurokinin B [NKB]) and calcitonin gene-related peptide (CGRP) in plasma protein extravasation in rat abdominal skin.
• To explore the interactions between CGRP and other inflammatory mediators.

Main Methods:

• Administration of SP, NKA, NKB, physalaemin, and CGRP to rat abdominal skin.
• Assessment of plasma protein extravasation.
• Investigating the effects of various pretreatments (capsaicin, indomethacin, compound 48/80, neuropeptide Y, mepyramine, cimetidine) and streptozotocin-induced diabetes.
• Examining CGRP's interaction with histamine, ATP, adenosine, serotonin, bradykinin, and neurotensin.

Main Results:

• SP, NKA, and NKB induced extravasation at a threshold dose of approximately 1 pmol.
• CGRP alone caused minimal extravasation but significantly potentiated SP, NKA, NKB, and physalaemin-induced responses.
• CGRP's potentiation of SP-induced extravasation was not affected by capsaicin, indomethacin, or compound 48/80, but was reduced by neuropeptide Y or mepyramine/cimetidine, and abolished in diabetic rats.
• CGRP augmented histamine-induced extravasation, reduced ATP/adenosine effects, and did not alter serotonin, bradykinin, or neurotensin responses.

Conclusions:

• NKA and NKB are potential mediators of neurogenic plasma extravasation, alongside SP.
• CGRP may act as a mediator of antidromic vasodilation and potentiates tachykinin-induced extravasation, potentially augmenting neurogenic inflammation.
• The complex interactions of CGRP with various mediators suggest multiple mechanisms of action in inflammatory processes.