Document Detail


Homologous desensitization of calcitonin gene-related peptide-induced relaxation in rat intramural coronary arteries.
MedLine Citation:
PMID:  14729386     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the type of desensitization of calcitonin gene-related peptide (CGRP)-induced responses in rat isolated intramural coronary arteries using isometric myograph and FURA-2 technique. In coronary arteries precontracted with 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha (U46619), development of tachyphylaxis to CGRP is characterized by significant attenuation of CGRP-induced maximal reduction in the tension and [Ca2+](i) during the second CGRP concentration-response curve; however, there was no further reduction in the CGRP-induced maximum relaxation during the third CGRP concentration-response curve. There was no sign of tachyphylaxis to CGRP when CGRP concentration-response curves were recorded in 36 mM K+-depolarized coronary arteries contrary to the results obtained in 300 nM U46619-precontracted coronary arteries. Preincubation with colchicine did not prevent the development of tachyphylaxis to CGRP in U46619-precontracted coronary arteries, indicating no role for endocytosis. Development of tachyphylaxis to CGRP was completely abolished by preincubating the coronary arteries with 1 microM RO 31-8220, indicating a role for protein kinases. Pre-exposure of the coronary arteries to isoprenaline or forskolin did not attenuate the CGRP-induced relaxation in these vessels, indicating that the cAMP-protein kinase A (PKA) pathway is not involved. Like CGRP, the coronary arteries developed tachyphylaxis toward isoprenaline during the second exposure. However, there was no sign of tachyphylaxis to either forskolin or dibutyryl cAMP (dbcAMP) during the second exposure. In conclusion, these results suggest that development of tachyphylaxis to CGRP in U46619-precontracted coronary is related to CGRP receptor-mediated activation of protein kinase.
Authors:
Majid Sheykhzade; Niels C Berg Nyborg
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  484     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-19     Completed Date:  2004-09-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  91-101     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Ø, Copenhagen, Denmark. mash@dfh.dk
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcitonin Gene-Related Peptide / pharmacology*
Coronary Vessels / drug effects*,  physiology
Dose-Response Relationship, Drug
Male
Rats
Rats, Sprague-Dawley
Receptors, Calcitonin Gene-Related Peptide / agonists,  physiology
Vasodilation / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Receptors, Calcitonin Gene-Related Peptide; 83652-28-2/Calcitonin Gene-Related Peptide

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