| Role of G proteins in agonist-induced Ca2+ sensitization of tracheal smooth muscle. | |
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MedLine Citation:
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PMID: 9755107 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased sensitivity to intracellular Ca2+ concentration ([Ca2+]) is an important mechanism for agonist-induced contraction of airway smooth muscle, but the signal transduction pathways involved are uncertain. We studied Ca2+ sensitization with acetylcholine (ACh) and endothelin (ET)-1 in porcine tracheal smooth muscle by measuring contractions at a constant [Ca2+] in strips permeabilized with alpha-toxin or beta-escin. The peptide inhibitor G protein antagonist 2A (GP Ant-2A), which has selectivity for Gq over Gi, inhibited contractile responses to ET-1, ACh, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), but the proportional inhibition of ACh responses was less than that of ET-1. Pretreatment with pertussis toxin reduced ACh contractions but had no effect on those of ET-1 or GTPgammaS. Clostridium botulinum C3 exoenzyme, which inactivates Rho family monomeric G proteins, caused similar reductions in contractile responses to ACh, ET-1, and GTPgammaS. Farnesyltransferase inhibition, which inhibits Ras G proteins, reduced responses to ET-1. We conclude that the heterotrimeric G proteins Gq and Gi both contribute to Ca2+ sensitization by ACh, whereas ET-1 responses involve Gq but not Gi. Both Gq and Gi pathways likely involve Rho family small G proteins. A Ras-mediated pathway also contributes to Ca2+ sensitization by ET-1 in airway smooth muscle. |
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Authors:
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T L Croxton; B Lande; C A Hirshman |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 275 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1998 Oct |
Date Detail:
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Created Date: 1998-11-23 Completed Date: 1998-11-23 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: L748-55 Citation Subset: IM |
Affiliation:
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Departments of Environmental Health Sciences and Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ADP Ribose Transferases
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pharmacology Acetylcholine / pharmacology Animals Botulinum Toxins* Calcium / metabolism* Endothelin-1 / pharmacology Escin / pharmacology GTP-Binding Protein alpha Subunits, Gi-Go / metabolism GTP-Binding Proteins / metabolism* Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology Macromolecular Substances Muscle Contraction / drug effects, physiology* Muscle, Smooth / drug effects, physiology* Pertussis Toxin Signal Transduction / drug effects, physiology Swine Trachea / drug effects, physiology* Type C Phospholipases / pharmacology Virulence Factors, Bordetella / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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P01-HL-10342/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Botulinum Toxins; 0/Endothelin-1; 0/Macromolecular Substances; 0/Virulence Factors, Bordetella; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 51-84-3/Acetylcholine; 6805-41-0/Escin; 7440-70-2/Calcium; EC 2.4.2.-/ADP Ribose Transferases; EC 2.4.2.-/exoenzyme C3, Clostridium botulinum; EC 2.4.2.31/Pertussis Toxin; EC 3.1.4.-/Type C Phospholipases; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gi-Go |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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