Document Detail

Mechanism of carteolol-induced cytosolic Ca2+ mobilization in cultured vascular smooth muscle cells.
MedLine Citation:
PMID:  20416399     Owner:  NLM     Status:  MEDLINE    
An increase in cytosolic calcium concentration triggers intracellular signal transduction in vascular cells, which then regulates the vascular contraction. In the present study, the regulatory mechanism of carteolol on the intracellular free Ca(2+) ([Ca(2+)](i)) mobilization was investigated in cultured A7r5 vascular smooth muscle cells. The A7r5 cells were cultured and loaded with fura-2-AM, which was used as a Ca(2+) sensitive fluorescent probe. In both the presence and absence of external Ca(2+), carteolol increased [Ca(2+)](i) with a dose-dependent manner in A7r5 cells at concentrations between 608 microM and 6.08 microM. In a Ca(2+)-containing buffer, carteolol-induced [Ca(2+)](i) showed an initial peak followed by a secondary and persistent plateau. Pretreatment of the cells with La(3+), the plasma membrane Ca(2+) pump inhibitor, and nifedipine, a L-type Ca(2+) channel inhibitor, both partially restrained the carteolol-induced initial peak in [Ca(2+)](i) by 92% and 86%, respectively. Pretreatment of the cells with adrenoceptor antagonists, prazosin inhibited the [Ca(2+)](i) response by 80%, and propranolol enhanced the response by 61%. In the Ca(2+-)-free buffer, pretreatment of the cells with carteolol inhibited the endoplasmic reticulum Ca(2+) pump inhibitor of thapsigargin-induced [Ca(2+)](i) increase by 97%. Pretreatment of the cells with thapsigargin also inhibited the carteolol-induced [Ca(2+)](i) rise by 98%. The internal Ca(2+) release induced by the carteolol was partially inhibited by U73122 (phospholipase C inhibitor) and aristolochic acid, quinacrine (phospholipase A(2) inhibitors). After incubation of carteolol in the Ca(2+)-free buffer, the addition of CaCl(2) increased the Ca(2+) influx, implying that the release of Ca(2+) from internal stores further induced capacitative Ca(2+) entry. These results suggest that carteolol-induced [Ca(2+)](i) increase is mediated by the initial influx via the alpha(1)-adrenoceptor, L-type Ca(2+) channel, nonselective calcium entry channels and release of Ca(2+) from an intracellular store, which is mainly in the endoplasmic reticulum followed by capacitative Ca(2+) entry but decrease via the beta(2)-adrenoceptor. The intracellular Ca(2+) release was also modulated by phospholipase A(2), C-coupled events.
Kwou-Yeung Wu; Cheng-Hsien Chang; Hwei-Zu Wang; Show-Jen Hong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-20
Journal Detail:
Title:  Vascular pharmacology     Volume:  53     ISSN:  1879-3649     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:    2010 Sep-Oct
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-12-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-93     Citation Subset:  IM    
Copyright Information:
Copyright 2010. Published by Elsevier Inc.
Department of Ophthalmology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology*
Calcium / metabolism*
Calcium Signaling
Carteolol / pharmacology*
Cells, Cultured
Cytosol / metabolism*
Dose-Response Relationship, Drug
Estrenes / pharmacology
Myocytes, Smooth Muscle / drug effects*,  metabolism
Nifedipine / pharmacology
Phospholipases A / antagonists & inhibitors,  metabolism
Prazosin / pharmacology
Propranolol / pharmacology
Pyrrolidinones / pharmacology
Thapsigargin / pharmacology
Type C Phospholipases / antagonists & inhibitors,  metabolism
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Estrenes; 0/Pyrrolidinones; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 19216-56-9/Prazosin; 21829-25-4/Nifedipine; 51781-06-7/Carteolol; 525-66-6/Propranolol; 67526-95-8/Thapsigargin; 7440-70-2/Calcium; EC 3.1.1.-/Phospholipases A; EC 3.1.4.-/Type C Phospholipases

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