title: The adenosine A(1)-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements.
abstract: 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 purpose of this study was to determine the effect of a selective adenosine A(1)-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure. After a 2-h control period, seven pregnant ewes received a 1-h intravenous infusion of ethanol (1 g/kg maternal body wt), followed 1 h later by a 2-h fetal intravenous infusion of either 8-CPT (3.78 +/- 0.08 microg. kg(-1). min(-1)) or vehicle. Ethanol reduced the incidence of FBM from 44.0 +/- 10.4 to 2.7 +/- 1.3% (P < 0.05) and 51.2 +/- 7.6 to 11.9 +/- 5.0% (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 +/- 11%) and was not different from control throughout the rest of the experiment. Ethanol also decreased the incidence of both low-voltage electrocortical activity and eye movements, but there were no differences in the incidences of these behavioral parameters between the 8-CPT and vehicle groups throughout the experiment. These data are consistent with the hypothesis that adenosine, acting via A(1) receptors, may play a role in the mechanism of ethanol-induced inhibition of FBM.
authors.affiliation: Departments of Physiology and Obstetrics and Gynecology, Medical Research Council Group in Fetal and Neonatal Health and Development, University of Western Ontario, London, Ontario N6A 4V2.
authors.forename: C S
authors.initials: CS
authors.lastname: Watson
authors.forename: S E
authors.initials: SE
authors.lastname: White
authors.forename: J H
authors.initials: JH
authors.lastname: Homan
authors.forename: L
authors.initials: L
authors.lastname: Fraher
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
authors.forename: A D
authors.initials: AD
authors.lastname: Bocking
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D004562:Electrocardiography; D000431:Ethanol / Q000494:pharmacology*; D005133:Eye Movements; D005260:Female; D005312:Fetal Blood; D005324:Fetal Movement / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D005740:Gases / Q000097:blood; D006340:Heart Rate, Fetal; D006454:Hemoglobins / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D011247:Pregnancy; D058915:Purinergic P1 Receptor Antagonists; D012119:Respiration / Q000187:drug effects*; D012756:Sheep / Q000196:embryology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D005740:Gases; D006454:Hemoglobins; D058915:Purinergic P1 Receptor Antagonists; D019344:Lactic Acid; C053907:8-cyclopentyl-1,3-dimethylxanthine; D000431:Ethanol; D013806:Theophylline