Document Detail

Down-regulation of adenylate cyclase coupled to adrenomedullin receptor in vascular smooth muscle cells.
MedLine Citation:
PMID:  9718278     Owner:  NLM     Status:  MEDLINE    
Adrenomedullin activates receptor-mediated adenylate cyclase to cause vasorelaxation. To elucidate whether desensitization of adenylate cyclase coupled to vascular adrenomedullin receptors occurs, we studied the adenylate cyclase activity after treatment with rat adrenomedullin in cultured rat aortic vascular smooth muscle cells. Cyclic AMP (cAMP) generation induced by adrenomedullin was markedly decreased by pretreatment with adrenomedullin: a maximal reduction (approximately 80%) was induced after 2 h and persisted during 24 h. Desensitization was independent of protein kinase A, protein kinase C, protein tyrosine kinase or receptor sequestration, because pretreatment with either isoproterenol, forskolin, tetradecanoylphorbol acetate, cytochalasin D, or colchicine did not affect the adrenomedullin-stimulated cAMP response. Furthermore, preincubation with inhibitors for these protein kinases prior to pretreatment with adrenomedullin failed to affect the adrenomedullin-induced decrease in cAMP response following the second stimulation with adrenomedullin. The present results provide the evidence for the existence of desensitization of adenylate cyclase coupled to vascular adrenomedullin receptors.
H Iwasaki; S Eguchi; M Shichiri; F Marumo; Y Hirata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  352     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-10-26     Completed Date:  1998-10-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  131-4     Citation Subset:  IM    
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
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MeSH Terms
Adenylate Cyclase / metabolism*
Cells, Cultured
Cyclic AMP / biosynthesis
GTP-Binding Proteins / metabolism
Membrane Proteins / metabolism*
Muscle, Smooth, Vascular / cytology,  enzymology,  metabolism*
Rats, Wistar
Receptors, Peptide*
Reg. No./Substance:
0/Membrane Proteins; 0/Receptors, Peptide; 0/adrenomedullin receptor; 60-92-4/Cyclic AMP; EC 3.6.1.-/GTP-Binding Proteins; EC Cyclase

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