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PACAP-induced plasma extravasation in rat skin
L O Cardell1, P Stjärne, S J Wagstaff
1Cardiovascular Research Institute and Department of Medicine, University of California San Francisco, 94143-0130, USA.
Regulatory Peptides
|August 15, 1997
Summary
Pituitary adenylate cyclase activating peptide (PACAP) 38 and PACAP 27 are potent inducers of plasma extravasation in rat skin, acting partly through histamine release. Their potency is comparable to Substance P, a known inflammatory mediator.
Area of Science:
- Pharmacology
- Neuroendocrinology
- Inflammation Research
Background:
- Pituitary adenylate cyclase activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are members of the secretin-glucagon-VIP peptide family.
- Plasma extravasation is a key indicator of inflammation and vascular permeability.
- The role of PACAP and VIP in modulating vascular permeability requires further elucidation.
Purpose of the Study:
- To investigate the in vivo effects of PACAP 38, PACAP 27, and VIP on plasma extravasation in rat skin.
- To compare the potency and maximal effects of PACAP isoforms and VIP in inducing plasma extravasation.
- To explore the potential involvement of histamine receptors and cAMP pathways in PACAP-induced plasma extravasation.
Main Methods:
- Intradermal injections of varying concentrations of PACAP 38, PACAP 27, VIP, and Substance P in rat skin.
- Quantification of plasma extravasation using a dye leakage assay.
- Administration of H1 and H2 receptor antagonists (pyrilamine and cimetidine, respectively) to assess histamine receptor involvement.
- Injection of synthetic cAMP analogs (dibutyryl cAMP) and a cAMP-inducing drug (salbutamol) to investigate the cAMP pathway.
Main Results:
- PACAP 38, PACAP 27, and VIP induced concentration-dependent plasma extravasation in rat skin.
- PACAP 38 was the most potent inducer, followed by PACAP 27 and VIP, which showed equal potency.
- PACAP 38 and PACAP 27 induced maximal extravasation, which was greater than that induced by VIP.
- PACAP 38 was approximately 5 times less potent than Substance P.
- Pyrilamine significantly reduced PACAP 38-induced extravasation, while cimetidine had no effect.
- Neither synthetic cAMP nor cAMP-inducing drugs caused plasma extravasation.
Conclusions:
- PACAP 38 and PACAP 27 are potent inducers of plasma extravasation in rat skin.
- The observed plasma extravasation is, at least partially, mediated by histamine release via H1 receptors.
- A cAMP-mediated mechanism is unlikely to be directly involved in PACAP-induced plasma extravasation.