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J Appl Physiol 86: 1410-1420, 1999;
8750-7587/99 $5.00
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Vol. 86, Issue 4, 1410-1420, April 1999

Increased cerebral extracellular adenosine and decreased PGE2 during ethanol-induced inhibition of FBM

Carole S. Watson1, Susan E. White1, Jacobus H. Homan1, Karen A. Kimura2, James F. Brien2, Laurence Fraher3, John R. G. Challis4, and Alan D. Bocking1

1 Departments of Physiology and of Obstetrics and Gynaecology, Medical Research Council Group in Fetal and Neonatal Health and Development, 3 Departments of Medicine and Biochemistry, Lawson Research Institute, University of Western Ontario, London, Ontario N6A 4V2; 2 Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario K7L 3N6; and 4 Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Adenosine and PGE2 are neuromodulators, both of which inhibit fetal breathing movements (FBM). Although circulating PGE2 has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for adenosine has not been examined. The objective of this study was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE2 concentrations by using in utero microdialysis and to relate any changes to ethanol-induced inhibition of FBM. Dialysate samples were obtained from the fetal parietal cortex over 70 h after surgery to determine steady-state extracellular fluid adenosine and PGE2 concentrations. On each of postoperative days 3 and 4, after a 2-h baseline period, ewes received a 1-h infusion of ethanol (1 g/kg maternal body wt) or an equivalent volume of saline, and the fetus was monitored for a further 11 h with 30-min dialysate samples collected throughout. Immediately after surgery, dialysate PGE2 and adenosine concentrations were 3.7 ± 0.7 and 296 ± 127 nM, respectively. PGE2 did not change over the 70 h, whereas adenosine decreased to 59 ± 14 nM (P < 0.05) at 4 h and then remained unchanged. Ethanol decreased dialysate PGE2 concentration for 2 h (3.3 ± 0.3 to 1.9 ± 0.4 nM; P < 0.05) and increased adenosine concentration for 6 h (87 ± 13 to a maximum of 252 ± 59 nM, P < 0.05). Ethanol decreased FBM incidence from 47 ± 7 to 16 ± 5% (P < 0.01) for 8 h. Saline infusion did not change dialysate adenosine or PGE2 concentrations or FBM incidence. These data are consistent with the hypothesis that fetal cerebral adenosine, and not PGE2, is the primary mediator of ethanol-induced inhibition of FBM at 123 days of gestation in sheep.

microdialysis; fetal behavior; electrocortical activity; eye movements; prostaglandin E2; fetal breathing movements


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C. S. Watson, S. E. White, J. H. Homan, L. Fraher, J. F. Brien, and A. D. Bocking
The adenosine A1-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements
J Appl Physiol, October 1, 1999; 87(4): 1333 - 1338.
[Abstract] [Full Text] [PDF]


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