Characterisation of CGRP receptors in the human isolated middle meningeal artery

Gupta, Saurabh; Mehrotra, Swati; Avezaat, C. J. J.; Villalón, Carlos M.; Saxena, Pramod R.; MaassenVanDenBrink, Antoinette

doi:10.1016/j.lfs.2006.01.003

Cited by 48 publications

(34 citation statements)

References 31 publications

(49 reference statements)

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“…17 Another study reported that h-␣CGRP concentration-dependently (0.1 nmol to 1 mol; with a pEC 50 of approximately 8.5 [11.97] g/L) relaxed precontracted (KCl) human meningeal artery segments by 92%. 18 These data illustrate that different experimental conditions (e.g., change in preconstricting agent) can change the observed variables by more than 10-fold in in vitro models. Preclinical data can be used to get some idea of the potency of the compound, but in vivo data and data from other species may show wide variation in results.…”

Section: Effect Of Sumatriptan On Mma and Mcamentioning

confidence: 81%

Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers

Hansen²,

et al. 2010

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Section: Effect Of Sumatriptan On Mma and Mcamentioning

confidence: 81%

Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers

Hansen²,

et al. 2010

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“…As for CGRP which is a vasodilative substance, the diameter of MMA during the addition of CGRP was extended by more than 50% compared to the baseline in rats (2). On the other hand, the CGRP antagonist constricted the human MMA by 50-60% in vitro (5).…”

Section: Discussionmentioning

confidence: 97%

The Middle Meningial Artery during a Migraine Attack: 3T Magnetic Resonance Angiography Study

et al. 2009

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“…When the potency of telcagepant is compared with that of other CGRP receptor antagonists in human coronary arteries, telcagepant is more potent than CGRP 8 -37 and an early-generation small-molecule CGRP receptor antagonist, compound 1 (Edvinsson et al, 2001;Hasbak et al, 2003). Telcagepant displays a slightly lower potency than the intraveneous antimigraine CGRP receptor antagonist olcegepant in coronary arteries (pA 2 of 9.37) (Edvinsson et al, 2001;Gupta et al, 2006b), cerebral arteries (Edvinsson et al, 2002), and middle meningeal arteries (Gupta et al, 2006a) (dura mater).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Calcitonin Gene-Related Peptide Receptor Antagonist Telcagepant (MK-0974) in Human Isolated Coronary Arteries

Chan¹,

Edvinsson²,

Eftekhari³

et al. 2010

J Pharmacol Exp Ther

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The sensory neuropeptide calcitonin gene-related peptide (CGRP) plays a role in primary headaches, and CGRP receptor antagonists are effective in migraine treatment. CGRP is a potent vasodilator, raising the possibility that antagonism of its receptor could have cardiovascular effects. We therefore investigated the effects of the antimigraine CGRP receptor antagonist telcagepant on human isolated coronary arteries. Arteries with different internal diameters were studied to assess the potential for differential effects across the coronary vascular bed. The concentration-dependent relaxation responses to human ␣CGRP were greater in distal coronary arteries (i.d. 600 -1000 m; E max ϭ 83 Ϯ 7%) than proximal coronary arteries (i.d. 2-3 mm; E max ϭ 23 Ϯ 9%), coronary arteries from explanted hearts (i.d. 3-5 mm; E max ϭ 11 Ϯ 3%), and coronary arterioles (i.d. 200 -300 m; E max ϭ 15 Ϯ 7%). Telcagepant alone did not induce contraction or relaxation of these coronary blood vessels. Pretreatment with telcagepant (10 nM to 1 M) antagonized ␣CGRP-induced relaxation competitively in distal coronary arteries (pA 2 ϭ 8.43 Ϯ 0.24) and proximal coronary arteries and coronary arterioles (1 M telcagepant, giving pK B ϭ 7.89 Ϯ 0.13 and 7.78 Ϯ 0.16, respectively). ␣CGRP significantly increased cAMP levels in distal, but not proximal, coronary arteries, and this was abolished by pretreatment with telcagepant. Immunohistochemistry revealed the expression and colocalization of the CGRP receptor elements calcitonin-like receptor and receptor activity-modifying protein 1 in the smooth muscle cells in the media layer of human coronary arteries. These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions.

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Characterisation of CGRP receptors in the human isolated middle meningeal artery

Cited by 48 publications

References 31 publications

Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers

Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers

The Middle Meningial Artery during a Migraine Attack: 3T Magnetic Resonance Angiography Study

Characterization of the Calcitonin Gene-Related Peptide Receptor Antagonist Telcagepant (MK-0974) in Human Isolated Coronary Arteries

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