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 - Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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 - Animals
KW - Calcitonin Gene-Related Peptide
KW - Dura Mater
KW - Gene Expression Regulation
KW - Male
KW - RNA, Messenger
KW - Rats
KW - Rats, Sprague-Dawley
KW - Receptor, Serotonin, 5-HT1B
KW - Receptor, Serotonin, 5-HT1D
KW - Receptors, Serotonin
KW - Serotonin Receptor Agonists
KW - Trigeminal Ganglion
KW - Trigeminal Nuclei
U2 - 10.1016/j.pain.2012.01.005
DO - 10.1016/j.pain.2012.01.005
M3 - Journal article
C2 - 22305629
SN - 1872-6623
VL - 153
SP - 830
EP - 838
JO - Pain
JF - Pain
IS - 4
ER -