Characterization of CGRP1 and CGRP2 Receptor Subtypesa

Quirion, Rémi; Rossum, Denise van; Dumont, Yvan; St‐Pierre, Serge; Fournier, Alain

doi:10.1111/j.1749-6632.1992.tb22759.x

Cited by 171 publications

(74 citation statements)

References 32 publications

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“…Taken together, these results suggest that CGRP related systems contribute to both the development and maintenance of tolerance to spinal morphine. The CGRP receptor antagonist, CGRP , is well recognized as a competitive antagonist for the CGRP 1 receptor subtype (Dennis et al, 1990;Quirion et al, 1992). BIBN4096BS is a novel competitive, non-peptide CGRP 1 receptor antagonist (Doods et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Powell

Sutak

et al. 2000

British J Pharmacology

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108

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1 This study examined the eects of the peptide CGRP receptor antagonist CGRP and the newly-developed non-peptide CGRP receptor antagonist BIBN4096BS for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. 2 Repeated administration of intrathecal morphine (15 mg), once daily, produced a progressive decline of antinociceptive eect and an increase in the ED 50 value in the tail¯ick and paw pressure tests. Co-administration of CGRP 8-37 (4 mg) or BIBN4096BS (0.05, 0.1 mg) with morphine (15 mg) prevented the decline of antinociceptive eect and increase in ED 50 value in the tail¯ick test. Intrathecal administration of the CGRP receptor antagonists did not alter the baseline responses in either tests. Acute CGRP 8-37 also did not potentiate the acute actions of spinal morphine. 3 In animals rendered tolerant to intrathecal morphine, subsequent administration of CGRP (4 mg) with morphine (15 mg) partially restored the antinociceptive eect and ED 50 value of acute morphine, re¯ecting the reversal of tolerance. 4 Animals tolerant to intrathecal morphine expressed increased CGRP and substance P-like immunostaining in the dorsal horn of the spinal cord. The increase in CGRP, but not substance Plike immunostaining, was blocked by a co-treatment with CGRP 8-37 (4 mg). In animals already tolerant to morphine, the increase in CGRP but not substance P-like immunostaining was partially reversed by CGRP 8-37 (4 mg). 5 These data suggest that activation of spinal CGRP receptors contributes to both the development and expression of spinal opioid tolerance. CGRP receptor antagonists may represent a useful therapeutic approach for preventing as well as reversing opioid tolerance.

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Section: Discussionmentioning

confidence: 99%

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Powell

Sutak

et al. 2000

British J Pharmacology

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108

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“…On the basis of pharmacological criteria, it is known that CGRP may act mainly on CGRP 1 and CGRP 2 receptors (Arulmani et al 2004), with h-αCGRP 8-37 being a 10-fold more potent antagonist at CGRP 1 receptors than at CGRP 2 receptors (Quirion et al 1992 Gupta et al 2006a;Jansen-Olesen et al 2003;Oliver et al 2002). The results from our laboratory also advocate the presence of CGRP 1 receptors in human meningeal (Gupta et al 2006a) and coronary (Gupta et al 2006b) arteries, while in human distal coronary artery, there seems to be an additional population of CGRP receptors not complying with the current classification of CGRP 1 or CGRP 2 receptors (Gupta et al 2006b).…”

Section: Cgrp Receptorsmentioning

confidence: 99%

Current and prospective pharmacological targets in relation to antimigraine action

Mehrotra

Gupta

Chan

et al. 2008

Naunyn-Schmied Arch Pharmacol

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Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT 1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT 2 receptor antagonists, Ca 2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT 1-7 ), adrenergic (α 1 , α 2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP 2 ), adenosine (A 1 , A 2 , and A 3 ), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon.

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“…CGRP receptors belong to the family of G-protein-coupled receptors characterized by seven transmembrane helices (Chatterjee et al, 1993) and are subdivided into two types, designated CGRP 1 and CGRP 2 receptors (Quirion et al, 1992). An important progress has been made in the field of receptor cloning and signalling by demonstrating that CRLR (calcitonin receptor-like receptor), in association with receptor activity modifying proteins (RAMPs: RAMP1, RAMP2, RAMP3) determined the receptor affinity to CGRP and adrenmedullin, while calcitonin receptor in association with RAMPs determines amylin affinity (McLatchie et al, 1998;Muff et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries

Sheykhzade

Lind

Edvinsson

2004

British J Pharmacology

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1 We investigated the antagonistic effect of 1-piperidinecarboxamide, N-[2-[[5amino-l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1- [(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS) on the calcitonin gene-related peptide (CGRP)-induced responses by using isometric myograph and FURA-2 technique in human subcutaneous arteries removed in association with abdominal surgery. 2 BIBN4096BS, at the concentration of 1 pM, had no significant effect on the CGRP-induced relaxation in these vessels. 3 At the concentration of 10 pM, BIBN4096BS had a competitive antagonistic-like behaviour characterized by parallel rightward shift in the log CGRP concentration-tension curve with no depression of the E max . 4 At the higher concentrations (0.1 and 1 nM), BIBN4096BS had a concentration-dependent noncompetitive antagonistic effect on the CGRP-induced responses. 5 The efficacy and potency of CGRP was significantly greater in the smaller (lumen diameter B200 mm) human subcutaneous arteries compared to the larger ones. 6 The apparent agonist equilibrium dissociation constant, K A , for CGRP 1 receptors in the human subcutaneous arteries was approximately 1 nM. Analysis of the relationship between receptor occupancy and response to CGRP indicates that the receptor reserve is relatively small. 7 Using reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA sequences encoding the calcitonin receptor-like receptor, receptor activity modifying protein (RAMP1, RAMP2, RAMP3) and receptor component protein were demonstrated in human subcutaneous arteries, indicating the presence of CGRP 1 -like receptor and the necessary component for the receptor activation. 8 In conclusion, the inhibitory action of BIBN4096BS at the low concentration (10 pM) on the CGRP-tension curve (but not intracellular calcium concentration ([Ca 2 þ ] i ) resembles what is seen with a reversible competitive antagonist. However, at the higher concentrations (0.1 and 1 nM), BIBN4096BS acts as a selective noncompetitive inhibitor at CGRP 1 receptors in human subcutaneous arteries.

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Characterization of CGRP₁ and CGRP₂ Receptor Subtypesa

Cited by 171 publications

References 32 publications

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Current and prospective pharmacological targets in relation to antimigraine action

Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries

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