Document Detail


Coexpression of ligand-gated P2X and G protein-coupled P2Y receptors in smooth muscle. Preferential activation of P2Y receptors coupled to phospholipase C (PLC)-beta1 via Galphaq/11 and to PLC-beta3 via Gbetagammai3.
MedLine Citation:
PMID:  9468531     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
P2 receptor subtypes and their signaling mechanisms were characterized in dispersed smooth muscle cells. UTP and ATP stimulated inositol 1,4,5-triphosphate formation, Ca2+ release, and contraction that were abolished by U-73122 and guanosine 5'-O-(3-thio)diphosphate, and partly inhibited (50-60%) by pertussis toxin (PTX). ATP analogs (adenosine 5'-(alpha, beta-methylene)triphosphate, adenosine 5'-(beta, gamma-methylene)triphosphate, and 2-methylthio-ATP) stimulated Ca2+ influx and contraction that were abolished by nifedipine and in Ca2+-free medium. Micromolar concentrations of ATP stimulated both Ca2+ influx and Ca2+ release. ATP and UTP activated Gq/11 and Gi3 in gastric and aortic smooth muscle and heart membranes, Gq/11 and Gi1 and/or Gi2 in liver membranes, and Go and Gi1-3 in brain membranes. Phosphoinositide hydrolysis stimulated by ATP and UTP was mediated concurrently by Galphaq/11-dependent activation of phospholipase (PL) C-beta1 and Gbetagammai3-dependent activation of PLC-beta3. Phosphoinositide hydrolysis was partially inhibited by PTX or by antibodies to Galphaq/11, Gbeta, PLC-beta1, or PLC-beta3, and completely inhibited by the following combinations (PLC-beta1 and PLC-beta3 antibodies; Galphaq/11 and Gbeta antibodies; PLC-beta1 and Gbeta antibodies; PTX with either PLC-beta1 or Galphaq/11 antibody). The pattern of responses implied that P2Y2 receptors in visceral, and probably vascular, smooth muscle are coupled to PLC-beta1 via Galphaq/11 and to PLC-beta3 via Gbetagammai3. These receptors co-exist with ligand-gated P2X1 receptors activated by ATP analogs and high levels of ATP.
Authors:
K S Murthy; G M Makhlouf
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  273     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-03-19     Completed Date:  1998-03-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4695-704     Citation Subset:  IM    
Affiliation:
Departments of Medicine and Physiology, Medical College of Virginia, Richmond, Virginia 23298-0711, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Monophosphate / analogs & derivatives,  pharmacology
Adenosine Triphosphate / pharmacology
Amino Acid Sequence
Animals
Calcium / metabolism
GTP-Binding Proteins / chemistry,  metabolism*
Isoenzymes / metabolism*
Muscle Contraction / drug effects
Muscle, Smooth / metabolism*,  physiology
Phospholipase C beta
Rabbits
Receptors, Purinergic P2 / agonists,  metabolism*
Type C Phospholipases / metabolism*
Uridine Triphosphate / pharmacology
Grant Support
ID/Acronym/Agency:
DK-28300/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Receptors, Purinergic P2; 56-65-5/Adenosine Triphosphate; 61-19-8/Adenosine Monophosphate; 63-39-8/Uridine Triphosphate; 7440-70-2/Calcium; EC 3.1.4.-/Type C Phospholipases; EC 3.1.4.11/Phospholipase C beta; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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