Increased cerebral extracellular adenosine and decreased PGE(2) during ethanol-induced inhibition of FBM

Adenosine and PGE(2) are neuromodulators, both of which inhibit fetal breat hing movements (FBM). Although circulating PGE(2) has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine f etus, a role for adenosine has not been examined. The objective of this stu dy was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE(2) concentrations by using i n utero microdialysis and to relate any changes to ethanol-induced inhibiti on of FBM. Dialysate samples were obtained from the fetal parietal cortex o ver 70 h after surgery to determine steady-state extracellular fluid adenos ine and PGE(2) 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 mat ernal body wt) or an equivalent volume of saline, and the fetus was monitor ed for a further 11 h with 30-min dialysate samples collected throughout. I mmediately after surgery, dialysate PGE(2) and adenosine concentrations wer e 3.7 +/- 0.7 and 296 +/- 127 nM, respectively. PGE(2) 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 PGE(2) concentration for 2 h (3.3 +/- 0.3 to 1.9 +/- 0.4 nM; P < 0.05) and increased adenosine c oncentration 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 PGE(2) concentrat ions or FBM incidence. These data are consistent with the hypothesis that f etal cerebral adenosine, and not PGE(2), is the primary mediator of ethanol -induced inhibition of FBM at 123 days of gestation in sheep.