Pharmacological and expression profile of the prostaglandin I(2) receptor in the rat craniovascular system

Maja Myren; Jes Olesen; Saurabh Gupta

doi:10.1016/j.vph.2011.06.004

Pharmacological and expression profile of the prostaglandin I(2) receptor in the rat craniovascular system

Maja Myren, Jes Olesen, Saurabh Gupta

8 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Vascular Pharmacology
Volume	55
Issue number	1-3
Pages (from-to)	50-8
Number of pages	9
ISSN	1537-1891
DOIs	https://doi.org/10.1016/j.vph.2011.06.004
Publication status	Published - Jul 2011

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10.1016/j.vph.2011.06.004

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@article{7e3421dc02e640b58c66163ce419c067,

title = "Pharmacological and expression profile of the prostaglandin I(2) receptor in the rat craniovascular system",

abstract = "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.",

author = "Maja Myren and Jes Olesen and Saurabh Gupta",

year = "2011",

month = jul,

doi = "10.1016/j.vph.2011.06.004",

language = "English",

volume = "55",

pages = "50--8",

journal = "Vascular Pharmacology",

issn = "1537-1891",

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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

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 -

Pharmacological and expression profile of the prostaglandin I(2) receptor in the rat craniovascular system

Abstract

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