A selective adenosine a1 receptor antagonist, 8-cpt, reverses
ethanol-induced inhibition of fetal breathing movements in sheep.
Watson, C. S., S. E. White, J. H. Homan, L. Fraher, J. F. Brien and A.
D. Bocking.
1Departments of Physiology and Obstetrics & Gynecology, MRC Group
in Fetal and Neonatal Health and Development, 2Departments of
Medicine and Biochemistry; 1,2Lawson Research Institute, University
of Western Ontario, London, Ontario, N6A 4V2 and 3Department of
Pharmacology and Toxicology, Queen's University, Kingston, Ontario,
K7L 3N6
APStracts 6:0281A, 1999.
Administration of either ethanol or adenosine inhibits fetal breathing
movements (FBM), eye movements and low-voltage electrocortical
activity (LV ECoG). The concentration of adenosine in ovine fetal
cerebral extracellular fluid increases during ethanol-induced
inhibition of FBM. The objective of this study was to determine the
effect of a selective adenosine A1 receptor antagonist, 8
-cyclopentyltheophylline (8-CPT) on the incidence of FBM during
ethanol exposure. After a 2-h control period, 7 pregnant ewes
received a 1-h intravenous infusion of ethanol (1 g/kg maternal body
weight) followed 1-hr later by a 2-h fetal intravenous infusion of
either 8-CPT (3.78[angstrom]a0.08 *g/kg/min) or vehicle. Ethanol
reduced the incidence of FBM from 44.0[angstrom]a10.4% to
2.7[angstrom]a1.3% (p<0.05) and 51.2[angstrom]a7.6% to
11.9%[angstrom]a5.0% (p<0.05), in fetuses destined to receive 8-CPT
or vehicle, respectively. In the vehicle group, FBM remained
suppressed for 7 h. In contrast, during the first hour of 8-CPT
infusion, FBM returned to baseline (31[angstrom]a11%) and was not
different from control throughout the rest of the experiment. Ethanol
also decreased the incidence of both LV ECoG and eye movements, but
there were no differences in the incidences of these behavioural
parameters between the 8-CPT and vehicle groups throughout the
experiment. These data are consistent with the hypothesis that
adenosine, acting via A1 receptors, may play a role in the mechanism
of ethanol- induced inhibition of FBM.
Received 18 June 1998; accepted in final form 26 May 1999.
APS Manuscript Number A543-8.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999