Abstract

BACKGROUND
Pituitary adenylate cyclase activating peptide-38 (PACAP-38) has been shown to induce migraine in migraineurs, whereas the related peptide vasoactive intestinal peptide (VIP) does not. In the present study we examine the hypothesis that PACAP-38 and its truncated version PACAP-27 but not VIP cause degranulation of mast cells in peritoneum and in dura mater.
METHODS
The degranulatory effects of PACAP-38, PACAP-27 and VIP were investigated by measuring the amount of N-acetyl-β-hexosaminidase released from isolated peritoneal mast cells and from dura mater attached to the skull of the rat in vitro. In peritoneal mast cells N-truncated fragments of PACAP-38 (PACAP(6-38), PACAP(16-38) and PACAP(28-38)) were also studied. To investigate transduction pathways involved in mast cell degranulation induced by PACAP-38, PACAP-27 and VIP, the phospholipase C inhibitor U-73122 and the adenylate cyclase inhibitor SQ 22536 were used.
RESULTS
The peptides induced degranulation of isolated peritoneal mast cells of the rat with the following order of potency: PACAP-38 = PACAP(6-38) = PACAP(16-38) » PACAP-27 = VIP = PACAP(28-38). In the dura mater we found that 10(-5) M PACAP-38 was significantly more potent in inducing mast cell degranulation than the same concentration of PACAP-27 or VIP. Inhibition of intracellular mechanisms demonstrated that PACAP-38-induced degranulation is mediated by the phospholipase C pathway. Selective blockade of the PAC(1) receptor did not attenuate degranulation.
CONCLUSION
These findings correlate with clinical studies and support the hypothesis that mast cell degranulation is involved in PACAP-induced migraine. PACAP-38 has a much stronger degranulatory effect on rat peritoneal and dural mast cells than VIP and PACAP-27. The difference in potency between PACAP-38- and PACAP-27/VIP-induced peritoneal mast cell degranulation is probably not related to the PAC(1) receptor but is caused by a difference in efficacy on phospholipase C.

Links

Publisher Full Text

Authors

Baun M, Pedersen MH, Olesen J, Jansen-Olesen I

Institution

Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark.

Source

Cephalalgia : an international journal of headache 32:4 2012 Mar pg 337-45

MeSH

Animals
Cell Degranulation
Disease Models, Animal
Dura Mater
Male
Mast Cells
Migraine Disorders
Peptides
Pituitary Adenylate Cyclase-Activating Polypeptide
Rats
Rats, Sprague-Dawley
Vasoactive Intestinal Peptide
Vasodilator Agents

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22421901