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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-2-2
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pubmed:abstractText |
The growth hormone secretagogue receptor subtype 1a (GHSR-1a) is involved in biological actions of ghrelin by triggering intracellular second messengers coupled to heterotrimeric G-protein complex involving Galpha(q/11). Adenosine is a partial agonist of the GHSR-1a, binding to a binding pocket distinct from the one described for ghrelin. This suggests a variety of functions for the poorly understood GHSR1a receptor. In this work, a sequential analysis of the pathways involved in the regulation of GHSR-1a signaling was undertaken to characterize the intracellular calcium mobilization that is observed following adenosine binding. The results showed that adenosine induced, in a dose-dependent manner, a calcium mobilization from IP(3)-sensitive intracellular stores since the IP(3) receptor blocker 2-APB was able to suppress the calcium response. However, adenosine did not show any effect in the formation of inositol phosphates. The calcium-mobilizing activity was blocked after preincubation of cells with CTX, the inhibitor of adenylate cyclase MDL-12,330A and the protein kinase A blocker H-89. Furthermore, the administration of adenosine stimulated cAMP production. Based on the experimental data, a signaling pathway is proposed involving adenylate cyclase and protein kinase A, which causes phosphorylation of the IP(3) receptor, with a cross-talk between the signaling pathways activated by ghrelin and adenosine. The data described in this report suggest that GHSR-1a is able to activate different intracellular second-messenger systems depending on the agonist that activates it. The regulation of the ghrelin-activated earliest signaling pathways by adenosine may have unexpected implications in the GHSR-1a actions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-aminoethoxydiphenyl borate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Boron Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ghrelin,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Metals, Heavy,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Ghrelin,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0028-3835
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2004 S. Karger AG, Basel
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pubmed:issnType |
Print
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13-25
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14755130-Adenosine,
pubmed-meshheading:14755130-Adjuvants, Immunologic,
pubmed-meshheading:14755130-Analysis of Variance,
pubmed-meshheading:14755130-Boron Compounds,
pubmed-meshheading:14755130-Calcium,
pubmed-meshheading:14755130-Cell Line,
pubmed-meshheading:14755130-Cholera Toxin,
pubmed-meshheading:14755130-Cyclic AMP,
pubmed-meshheading:14755130-Dose-Response Relationship, Drug,
pubmed-meshheading:14755130-Drug Interactions,
pubmed-meshheading:14755130-Embryo, Mammalian,
pubmed-meshheading:14755130-Enzyme Inhibitors,
pubmed-meshheading:14755130-Extracellular Space,
pubmed-meshheading:14755130-Ghrelin,
pubmed-meshheading:14755130-Humans,
pubmed-meshheading:14755130-Inositol Phosphates,
pubmed-meshheading:14755130-Iodine Isotopes,
pubmed-meshheading:14755130-Kidney,
pubmed-meshheading:14755130-Metals, Heavy,
pubmed-meshheading:14755130-Peptide Hormones,
pubmed-meshheading:14755130-Pertussis Toxin,
pubmed-meshheading:14755130-Radioligand Assay,
pubmed-meshheading:14755130-Receptors, G-Protein-Coupled,
pubmed-meshheading:14755130-Receptors, Ghrelin,
pubmed-meshheading:14755130-Signal Transduction,
pubmed-meshheading:14755130-Thapsigargin,
pubmed-meshheading:14755130-Transfection,
pubmed-meshheading:14755130-Type C Phospholipases,
pubmed-meshheading:14755130-Vasodilator Agents
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pubmed:year |
2004
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pubmed:articleTitle |
Agonist-specific coupling of growth hormone secretagogue receptor type 1a to different intracellular signaling systems. Role of adenosine.
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pubmed:affiliation |
Department of Medicine, Research Area, Molecular Endocrinology Laboratory, Complejo Hospitalario Universitario de Santiago (CHUS) and University of Santiago de Compostela, Santiago de Compostela, Spain.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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