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Table of Contents
Vol. 79, No. 1, 2004
Issue release date: January 2004
Section title: Regulation of Growth Hormone
Neuroendocrinology 2004;79:13–25
(DOI:10.1159/000076042)

Agonist-Specific Coupling of Growth Hormone Secretagogue Receptor Type 1a to Different Intracellular Signaling Systems

Role of Adenosine

Carreira M.C.a · Camiña J.P.a · Smith R.G.b · Casanueva F.F.a
aDepartment of Medicine, Research Area, Molecular Endocrinology Laboratory, Complejo Hospitalario Universitario de Santiago (CHUS) and University of Santiago de Compostela, Santiago de Compostela, Spain; bHuffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tex., USA

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Article / Publication Details

First-Page Preview
Abstract of Regulation of Growth Hormone

Received: July 24, 2003
Accepted: November 27, 2003
Published online: February 02, 2004
Issue release date: January 2004

Number of Print Pages: 13
Number of Figures: 10
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

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 Gαq/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 IP3-sensitive intracellular stores since the IP3 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 IP3 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.

© 2004 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Regulation of Growth Hormone

Received: July 24, 2003
Accepted: November 27, 2003
Published online: February 02, 2004
Issue release date: January 2004

Number of Print Pages: 13
Number of Figures: 10
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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