TY - JOUR
T1 - PACAP and its receptors in cranial arteries and mast cells
AU - Jansen-Olesen, Inger
AU - Hougaard Pedersen, Sara
PY - 2018
Y1 - 2018
N2 - BACKGROUND: In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion of the closely related vasoactive intestinal peptide (VIP) either induces headache or flushing. This implicates the pituitary adenylate cyclase activating peptide type I receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked headaches. Here we review studies characterizing the effects of mainly PACAP but also of VIP on cerebral and meningeal arteries and mast cells.DISCUSSION: PACAP1-38, PACAP1-27 and VIP dilate cerebral and meningeal arteries from several species including man. In rat cerebral and meningeal arteries the dilation seems to be mediated preferably via vasoactive intestinal peptide receptor type 1 (VPAC1) receptors while, in human, middle meningeal artery dilation induced via vasoactive intestinal peptide receptor type 2 (VPAC2) receptors cannot be ruled out. PACAP1-38 is a strong degranulator of peritoneal and dural mast cells while PACAP1-27 and VIP only have weak effects. More detailed characterization studies suggest that mast cell degranulation is not mediated via the known receptors for PACAP1-38 but rather via a still unknown receptor coupled to phospholipase C.CONCLUSION: It is suggested that PACAP1-38 might induce migraine via degranulation of dural mast cells via a yet unknown receptor.
AB - BACKGROUND: In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion of the closely related vasoactive intestinal peptide (VIP) either induces headache or flushing. This implicates the pituitary adenylate cyclase activating peptide type I receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked headaches. Here we review studies characterizing the effects of mainly PACAP but also of VIP on cerebral and meningeal arteries and mast cells.DISCUSSION: PACAP1-38, PACAP1-27 and VIP dilate cerebral and meningeal arteries from several species including man. In rat cerebral and meningeal arteries the dilation seems to be mediated preferably via vasoactive intestinal peptide receptor type 1 (VPAC1) receptors while, in human, middle meningeal artery dilation induced via vasoactive intestinal peptide receptor type 2 (VPAC2) receptors cannot be ruled out. PACAP1-38 is a strong degranulator of peritoneal and dural mast cells while PACAP1-27 and VIP only have weak effects. More detailed characterization studies suggest that mast cell degranulation is not mediated via the known receptors for PACAP1-38 but rather via a still unknown receptor coupled to phospholipase C.CONCLUSION: It is suggested that PACAP1-38 might induce migraine via degranulation of dural mast cells via a yet unknown receptor.
KW - Animals
KW - Cell Degranulation/drug effects
KW - Humans
KW - Mast Cells/drug effects
KW - Meningeal Arteries/drug effects
KW - Migraine Disorders/metabolism
KW - Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism
KW - Pituitary Gland/drug effects
KW - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism
KW - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/metabolism
KW - Receptors, Vasoactive Intestinal Peptide, Type II/metabolism
KW - Receptors, Vasoactive Intestinal Polypeptide, Type I/metabolism
KW - Signal Transduction/drug effects
KW - Vasoactive Intestinal Peptide/metabolism
U2 - 10.1186/s10194-017-0822-2
DO - 10.1186/s10194-017-0822-2
M3 - Review
C2 - 29460121
SN - 1129-2377
VL - 19
SP - 16
JO - The Journal of Headache and Pain Online
JF - The Journal of Headache and Pain Online
IS - 1
ER -