TY - JOUR
T1 - MRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system
AU - Amrutkar, Dipak V.
AU - Ploug, Kenneth B.
AU - Hay-Schmidt, Anders
AU - Porreca, Frank
AU - Olesen, Jes
AU - Jansen-Olesen, Inger
N1 - Funding Information:
This study was supported by Candy’s Foundation , The Lundbeck Foundation , The Lundbeck Foundation as part of the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS), and by the Aase and Ejnar Danielsen Foundation and the A.P. Møller Foundation for the advancement of Medical Sciences.
PY - 2012/4
Y1 - 2012/4
N2 - Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT 1 receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expression of these receptors and the role of 5-HT 1 receptor subtypes in controlling the release of calcitonin gene-related peptide (CGRP) in rat dura mater, trigeminal ganglion (TG), and trigeminal nucleus caudalis (TNC). The mRNA for each receptor subtype was quantified by quantitative real-time polymerase chain reaction. A high potassium concentration was used to release CGRP from dura mater, isolated TG, and TNC in vitro. The immunoreactive CGRP (iCGRP) release was measured by enzyme-linked immunoassay. The mRNA transcripts of the 3 5-HT 1 receptor subtypes were detected in the trigeminovascular system. Sumatriptan inhibited iCGRP release by 31% in dura mater, 44% in TG, and 56% in TNC. This effect was reversed by a 5-HT 1B/1D antagonist (GR127395). The 5-HT 1F agonist (LY-344864) was effective in the dura mater (26% iCGRP inhibition), and the 5-HT 1D agonist (PNU-142633) had a significant effect in the TNC (48%), whereas the 5-HT 1B agonist (CP-94253) was unable to reduce the iCGRP release in all tissues studied. We found that sumatriptan reduced the iCGRP release via activation of 5-HT 1D and 5-HT 1F receptor subtypes. The 5-HT 1F receptor agonist was effective only in peripheral terminals in dura mater, whereas the 5-HT 1D agonist had a preferential effect on central terminals in the TNC.
AB - Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT 1 receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expression of these receptors and the role of 5-HT 1 receptor subtypes in controlling the release of calcitonin gene-related peptide (CGRP) in rat dura mater, trigeminal ganglion (TG), and trigeminal nucleus caudalis (TNC). The mRNA for each receptor subtype was quantified by quantitative real-time polymerase chain reaction. A high potassium concentration was used to release CGRP from dura mater, isolated TG, and TNC in vitro. The immunoreactive CGRP (iCGRP) release was measured by enzyme-linked immunoassay. The mRNA transcripts of the 3 5-HT 1 receptor subtypes were detected in the trigeminovascular system. Sumatriptan inhibited iCGRP release by 31% in dura mater, 44% in TG, and 56% in TNC. This effect was reversed by a 5-HT 1B/1D antagonist (GR127395). The 5-HT 1F agonist (LY-344864) was effective in the dura mater (26% iCGRP inhibition), and the 5-HT 1D agonist (PNU-142633) had a significant effect in the TNC (48%), whereas the 5-HT 1B agonist (CP-94253) was unable to reduce the iCGRP release in all tissues studied. We found that sumatriptan reduced the iCGRP release via activation of 5-HT 1D and 5-HT 1F receptor subtypes. The 5-HT 1F receptor agonist was effective only in peripheral terminals in dura mater, whereas the 5-HT 1D agonist had a preferential effect on central terminals in the TNC.
KW - CGRP
KW - Migraine
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U2 - 10.1016/j.pain.2012.01.005
DO - 10.1016/j.pain.2012.01.005
M3 - Article
C2 - 22305629
AN - SCOPUS:84858708976
SN - 0304-3959
VL - 153
SP - 830
EP - 838
JO - Pain
JF - Pain
IS - 4
ER -