HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/R693    most recent 90363.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Maeda, T. Articles by Koos, B. J. Search for Related Content PubMed PubMed Citation Articles by Maeda, T. Articles by Koos, B. J.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Adenosine A₁ and A_2a receptors modulate insulinemia, glycemia, and lactatemia in fetal sheep

Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology; and The Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California

Submitted 16 April 2008 ; accepted in final form 28 December 2008

Adenosine A₁ and A_2A receptor subtypes modulate metabolism in adult mammals. This study was designed to determine the role of these receptors in regulating plasma levels of insulin, glucose, and lactate in 20 chronically catheterized fetal sheep (>0.8 term). In normoxic fetuses (Pa_O2 24 Torr), systemic blockade of A₁ receptors with DPCPX (n = 6) increased plasma concentrations of insulin, glucose, and lactate, but antagonism of A_2A receptors with ZM-241385 (n = 5) had no significant effects. Intravascular administration of adenosine (n = 9) reduced insulin concentrations and elevated glucose and lactate levels. DPCPX (n = 6) augmented the glycemic and lactatemic responses of adenosine. In contrast, ZM241385 (n = 5) virtually abolished adenosine-induced hyperglycemia and hyperlactatemia. Isocapnic hypoxia (Pa_O2 13 Torr) suppressed insulinemia and enhanced glycemia and lactatemia, but only the hyperglycemia was blunted by blockade of A₁ (n = 6) or A_2A (n = 6) receptors. We conclude that 1) endogenous adenosine via A₁ receptors depresses plasma concentrations of insulin, glucose, and lactate; 2) exogenous adenosine via A_2A receptors increases glucose and lactate levels, but these responses are dampened by stimulation of A₁ receptors; and 3) hypoxia, which increases endogenous adenosine concentrations, induces hyperglycemia that is partly mediated by activation of A₁ and A_2A receptors. We predict that adenosine, via A₁ receptors, facilitates at least 12% of glucose uptake and utilization in normoxic fetuses.

fetus; hypoxia; metabolism; growth; placenta