Suppressive action of endogenous adenosine on ovine fetal
nonshivering thermogenesis.
Ball, Karen T., Tania R. Gunn, Peter D. Gluckman, and Gordon G. Power.
Center for Perinatal Biology, School of Medicine, Loma Linda
University, Loma Linda, California 92350 and Department of
Pediatrics, School of Medicine, University of Auckland, Auckland, New
Zealand
APStracts 3:0408A, 1996.
Nonshivering thermogenesis is not initiated when the fetal sheep is
cooled in utero, but appears to require the removal of an inhibitor
of placental origin at birth. To test whether adenosine is such an
inhibitor, we examined the effect of the adenosine antagonist
theophylline on the initiation of nonshivering thermogenesis during
sequential cooling, ventilation and umbilical cord occlusion in
utero. Theophylline (18 mg/kg bolus and 0.6 mg/kg per min thereafter)
was infused for 90 min before and 90 min after cord occlusion.
Theophylline enhanced the nonshivering thermogenic free fatty acid
(FFA) and glycerol responses prior to cord occlusion, raising FFA
concentrations 99% to 415 +/- 60 [mu]Eq/l (P < 0.01) and
glycerol levels 87% to 526 +/- 135 [mu]mol/l (P< 0.05). These
FFA (P < 0.001) and glycerol (P < 0.05) concentrations were
significantly greater than the corresponding period during the birth
simulation control. Umbilical cord occlusion did not alter FFA
levels, but induced a 41% rise in glycerol concentrations to 774 +/-
203 [mu]mol/l (P < 0.05). The increases in nonshivering
thermogenic indices after the administration of the adenosine
-receptor antagonist suggest that the quiescent state of ovine fetal
brown adipose tissue may result, in part, from the tonic inhibitory
actions of adenosine and that a decrease in adenosine concentrations
enhances nonshivering thermogenesis. However, the further rise after
umbilical cord occlusion suggests that at least one other inhibitor
of placental origin inhibits nonshivering thermogenesis before birth.
Received 19 May 1995; accepted in final form 6 August 1996.
APS Manuscript Number A517-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996