TY - JOUR
T1 - Pharmacological and expression profile of the prostaglandin I(2) receptor in the rat craniovascular system
AU - Myren, Maja
AU - Olesen, Jes
AU - Gupta, Saurabh
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/7
Y1 - 2011/7
N2 - Activation of the trigeminal nerve terminals around cerebral and meningeal arteries is thought to be an important patho-mechanism in migraine. Vasodilatation of the cranial arteries may also play a role in increasing nociception. Prostaglandin I 2 (PGI 2) is capable of inducing a headache in healthy volunteers, a response that is likely to be mediated by the prostaglandin I 2 receptor (IP). This study investigates the functional and molecular characteristics of the IP receptor in the rat craniovascular system. In the closed cranial window model, iloprost, an IP receptor agonist, dilated the rat middle meningeal artery (MMA) (E max=170%±16%; pED 50=6.5±0.2) but not the rat cerebral artery (CA) in vivo. The specific antagonist of the IP receptor, CAY10441, significantly blocked the iloprost-induced response dose-dependently, with the highest dose attenuating iloprost (1μgkg -1) induced dilatations by 70% (p<0.05). CAY10441 did not have any effect on the prostaglandin E 2-induced vasodilatory response, thus suggesting no interaction with EP 2 and EP 4 receptors. IP receptor mRNA transcripts and protein were present in meningeal as well as in cerebral rat vasculature, and localized the IP receptor protein to the smooth vasculature of the cranial arteries (MMA, MCA and basilar artery). Together, these results demonstrate that the IP receptor mediates the dilatory effect of PGI 2 in the cranial vasculature in rats. Antagonism of this receptor might be of therapeutic relevance in acute migraine treatment.
AB - Activation of the trigeminal nerve terminals around cerebral and meningeal arteries is thought to be an important patho-mechanism in migraine. Vasodilatation of the cranial arteries may also play a role in increasing nociception. Prostaglandin I 2 (PGI 2) is capable of inducing a headache in healthy volunteers, a response that is likely to be mediated by the prostaglandin I 2 receptor (IP). This study investigates the functional and molecular characteristics of the IP receptor in the rat craniovascular system. In the closed cranial window model, iloprost, an IP receptor agonist, dilated the rat middle meningeal artery (MMA) (E max=170%±16%; pED 50=6.5±0.2) but not the rat cerebral artery (CA) in vivo. The specific antagonist of the IP receptor, CAY10441, significantly blocked the iloprost-induced response dose-dependently, with the highest dose attenuating iloprost (1μgkg -1) induced dilatations by 70% (p<0.05). CAY10441 did not have any effect on the prostaglandin E 2-induced vasodilatory response, thus suggesting no interaction with EP 2 and EP 4 receptors. IP receptor mRNA transcripts and protein were present in meningeal as well as in cerebral rat vasculature, and localized the IP receptor protein to the smooth vasculature of the cranial arteries (MMA, MCA and basilar artery). Together, these results demonstrate that the IP receptor mediates the dilatory effect of PGI 2 in the cranial vasculature in rats. Antagonism of this receptor might be of therapeutic relevance in acute migraine treatment.
U2 - 10.1016/j.vph.2011.06.004
DO - 10.1016/j.vph.2011.06.004
M3 - Journal article
C2 - 21749934
SN - 1537-1891
VL - 55
SP - 50
EP - 58
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 1-3
ER -