Dural mast cell degranulation is a putative mechanism for headache induced by PACAP-38.
Cephalalgia
; 32(4): 337-45, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22421901
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-ß-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) ¼ 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vasodilatadores
/
Degranulação Celular
/
Dura-Máter
/
Polipeptídeo Hipofisário Ativador de Adenilato Ciclase
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Mastócitos
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Transtornos de Enxaqueca
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article