UM
Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture
Takhshid M.A.1; Poyner D.R.3; Chabot J.-G.2; Fournier A.4; Ma W.2; Zheng W.-H.2; Owji A.A.2; Quirion R.2
2006-06-08
Source PublicationBritish Journal of Pharmacology
ISSN00071188 14765381
Volume148Issue:4Pages:459-468
Abstract1 Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) have structural similarities, interact with each others receptors (calcitonin receptor-like receptor (CLR)/receptor-activity-modifying proteins (RAMPs)) and show overlapping biological activities. AM and CGRP receptors are chiefly coupled to cAMP production. In this study, a method of primary dissociated cell culture was used to investigate the presence of AM and CGRP receptors and their effects on cAMP production in embryonic spinal cord cells. 2 Both neuronal and non-neuronal CLR immunopositive cells were present in our model. 3 High affinity, specific [ I]-AM binding sites (K(d) 79±9 pM and B(max) 571±34 fmol mg protein) were more abundant than specific [ I]-CGRP binding sites (K(d) 12±0.7 pM and B(max) 32±2 fmol mg protein) in embryonic spinal cord cells. 4 Specific [ I]-AM binding was competed by related molecules with a ligand selectivity profile of rAM>hAM(22-52)>rCGRPα>CGRP(8-37) ≫[r-(r*,s*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl] carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide (BIBN4096BS). 5 Specific [ I]-CGRP binding was competed by rCGRPα>rAM≥ CGRP(8-37)≥BIBN4096BS>hAM(22-52). 6 Cellular levels of cAMP were increased by AM (pEC"5"0 10.2±0.2) and less potently by rCGRPα (pEC"5"0 8.9±0.4). rCGRPα-induced cAMP accumulation was effectively inhibited by CGRP(8-37) (pA"2 7.63±0.44) and hAM(22-52) (pA"2 6.18±0.21) while AM-stimulation of cAMP levels was inhibited by CGRP(8-37) (pA"2 7.41±0.15) and AM(22-52) (pA"2 7.26±0.18). BIBN4096BS only antagonized the effects of CGRP (pA"2 8.40±0.30) on cAMP accumulation. 7 These pharmacological profiles suggest that effects of CGRP are mediated by the CGRP"1 (CLR/RAMP1) receptor in our model while those of AM are related to the activation of the AM"1 (CLR/RAMP2) receptor subtype. © 2006 Nature Publishing Group All rights reserved.
KeywordAdrenomedullin BIBN4096BS Calcitonin gene-related peptide Calcitonin receptor-like receptor cAMP CGRP Receptor binding assays Receptor-activity-modifying protein Spinal cord
DOI10.1038/sj.bjp.0706750
URLView the original
Language英語
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Shiraz University of Medical Sciences
2.Douglas Hospital Research Center
3.Aston University
4.INRS-Institut Armand Frappier
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GB/T 7714
Takhshid M.A.,Poyner D.R.,Chabot J.-G.,et al. Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture[J]. British Journal of Pharmacology,2006,148(4):459-468.
APA Takhshid M.A..,Poyner D.R..,Chabot J.-G..,Fournier A..,Ma W..,...&Quirion R..(2006).Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture.British Journal of Pharmacology,148(4),459-468.
MLA Takhshid M.A.,et al."Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture".British Journal of Pharmacology 148.4(2006):459-468.
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