title: Effect of PGD2on middle meningeal artery and mRNA expression profile of L-PGD2synthase and DP receptors in trigeminovascular system and other pain processing structures in rat brain.
abstract: BACKGROUND
  Prostaglandins (PGs), particularly prostaglandin D2(PGD2), E2(PGE2), and I2(PGI2), are considered to play a role in migraine pain. In humans, infusion of PGD2causes lesser headache as compared to infusion of PGE2and PGI2. Follow-up studies in rats have shown that infusion of PGE2and PGI2dilate the middle meningeal artery (MMA), and mRNA for PGE2and PGI2receptors is present in rat trigeminovascular system (TVS) and in the brain structures associated with pain. In the present study, we have characterized the dilatory effect of PGD2on rat MMA and studied the relative mRNA expression of PGD2receptors and lipocalin-type of PGD2synthase (L-PGDS).
  
  
  METHODS
  Rat closed-cranial window (CCW) model was used to study the effect of the DP1receptor antagonist, MK-0524, on PGD2-induced vasodilation of middle meningeal artery. The qPCR technique was used for mRNA expression analysis.
  
  
  RESULTS
  PGD2infusion evoked a dose-dependent dilation of the rat MMA. The calculated mean pED50value was 5.23±0.10 and Emaxwas 103±18% (n=5). MK-0524 significantly (∼61%, p<0.05) blocked the PGD2-induced dilation of MMA. mRNA for the DP1, DP2and L-PGDS were expressed differentially in all tested tissues. DP1receptor mRNA was expressed maximally in trigeminal ganglion (TG) and in cervical dorsal root ganglion (DRG).
  
  
  CONCLUSIONS
  High expression of DP1mRNA in the TG and DRG suggest that PGD2might play a role in migraine pathophysiology. Activation of the DP1receptor in MMA was mainly responsible for vasodilation induced by PGD2infusion.
authors.affiliation: Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: aysegulsekeroglu@gmail.com.
authors.forename: Aysegül
authors.initials: A
authors.lastname: Sekeroglu
authors.affiliation: Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: julie.mie.madsen@regionh.dk.
authors.forename: Julie Mie
authors.initials: JM
authors.lastname: Jacobsen
authors.affiliation: Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: inger.jansen-olesen@regionh.dk.
authors.forename: Inger
authors.initials: I
authors.lastname: Jansen-Olesen
authors.affiliation: Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: saugup01@gmail.com.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: mash@sund.ku.dk.
authors.forename: Majid
authors.initials: M
authors.lastname: Sheykhzade
authors.affiliation: Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: jes.olesen@regionh.dk.
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
authors.affiliation: Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: deepak.kumar.bhatt@regionh.dk.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Bhatt
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics*; D008576:Meningeal Arteries / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000235:genetics* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000096:biosynthesis / Q000235:genetics*; D059467:Transcriptome; D014278:Trigeminal Nuclei / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D054834:Lipocalins; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C501562:prostanoid D receptor 1, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2
keywords: DP(1) receptor; MK-0524; Middle meningeal artery; Migraine; Prostaglandin D(2); Vasodilation