mRNA expression profile of prostaglandin D2 receptors in rat trigeminovascular system, and effect of prostaglandins in rat migraine models
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mRNA expression profile of prostaglandin D2 receptors in rat trigeminovascular system, and effect of prostaglandins in rat migraine models. / Sekeroglu, A.; Jansen-Olesen, I.; Gupta, S.; Sheykhzade, M.; Bhatt, D.
In: Cephalalgia, Vol. 35, No. suppl 6S, PO446, 05.2015, p. 232-233.Research output: Contribution to journal › Conference abstract in journal › Research › peer-review
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T1 - mRNA expression profile of prostaglandin D2 receptors in rat trigeminovascular system, and effect of prostaglandins in rat migraine models
AU - Sekeroglu, A.
AU - Jansen-Olesen, I.
AU - Gupta, S.
AU - Sheykhzade, M.
AU - Bhatt, D.
PY - 2015/5
Y1 - 2015/5
N2 - Background: Prostaglandin D2 (PGD2) is a strong vasodilator of extracerebral arteries, but causes only mild headache in healthy volunteers. Aims: 1.) To elucidate the mRNA expression profile of DP1, DP2 receptors and PGD2 synthase (L-PGDS) in the trigeminovascular system (TVS); and other pain processing structures in rat brain; 2.) To study the effect of the DP1 receptor antagonist, MK-0524, on PGD2-induced vasodilation of middle meningeal artery (MMA) in rat closed cranial window (CCW) model; 3.) To investigate if an i.v. infusion of prostaglandin (PG) mix, PGD2, PGE2 and PGI2 (iloprost), in awake rats activates nociceptive/neuronal activation markers in the TVS. Methods: qPCR, the genuine rat CCW model, and the western blot technique were used to investigate the above mentioned aims. Results: mRNA for DP1, DP2 and L-PGDS was expressed differentially in all examined tissues. The DP1 receptor was highly expressed in trigeminal ganglion and dorsal rootganglion. MK-0524 significantly (62%, p<0.05) blocked the PGD2- induced dilation of MMA. No increase in p-ERK protein level was observed in the TVS after infusion of PG mix in awake rats. Neuronal activation markers, cFOS and EGR-1, were not changed in the trigeminal nucleus caudalis. Conclusions: PGD2 induced vasodilation of MMA is mainly mediated by activation of DP1 receptors. Furthermore, high expression of DP1 mRNA in TG and DRG suggest that PGD2 might play a role in migraine pathophysiology. However, infusion of PG mix in awake rats did not activate nociceptive/neuronal markers in the TVS.
AB - Background: Prostaglandin D2 (PGD2) is a strong vasodilator of extracerebral arteries, but causes only mild headache in healthy volunteers. Aims: 1.) To elucidate the mRNA expression profile of DP1, DP2 receptors and PGD2 synthase (L-PGDS) in the trigeminovascular system (TVS); and other pain processing structures in rat brain; 2.) To study the effect of the DP1 receptor antagonist, MK-0524, on PGD2-induced vasodilation of middle meningeal artery (MMA) in rat closed cranial window (CCW) model; 3.) To investigate if an i.v. infusion of prostaglandin (PG) mix, PGD2, PGE2 and PGI2 (iloprost), in awake rats activates nociceptive/neuronal activation markers in the TVS. Methods: qPCR, the genuine rat CCW model, and the western blot technique were used to investigate the above mentioned aims. Results: mRNA for DP1, DP2 and L-PGDS was expressed differentially in all examined tissues. The DP1 receptor was highly expressed in trigeminal ganglion and dorsal rootganglion. MK-0524 significantly (62%, p<0.05) blocked the PGD2- induced dilation of MMA. No increase in p-ERK protein level was observed in the TVS after infusion of PG mix in awake rats. Neuronal activation markers, cFOS and EGR-1, were not changed in the trigeminal nucleus caudalis. Conclusions: PGD2 induced vasodilation of MMA is mainly mediated by activation of DP1 receptors. Furthermore, high expression of DP1 mRNA in TG and DRG suggest that PGD2 might play a role in migraine pathophysiology. However, infusion of PG mix in awake rats did not activate nociceptive/neuronal markers in the TVS.
U2 - 10.1177/0333102415581304
DO - 10.1177/0333102415581304
M3 - Conference abstract in journal
VL - 35
SP - 232
EP - 233
JO - Cephalalgia
JF - Cephalalgia
SN - 0800-1952
IS - suppl 6S
M1 - PO446
ER -
ID: 140493517