The role of adenosine A1 receptor activation in ethanol-induced inhibition of stimulated glutamate release in the hippocampus of the fetal and adult guinea pig.
The role of adenosine A1 receptor activation in ethanol-induced inhibition of stimulated L-glutamate (Glu) release was determined in transverse hippocampal slices of the near-term fetal guinea pig and the adult guinea pig. Exposure of the slices to 48 mM ethanol inhibited K(+)-stimulated Glu efflux. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective adenosine A1 receptor antagonist, blocked the ethanol-induced inhibition of K(+)-stimulated Glu efflux in the near-term fetal and adult hippocampus. In the near-term fetus, 2-chloro-N6-cyclopentyladenosine (CCPA), a selective adenosine A1 agonist, and exogenous adenosine each blocked K(+)-stimulated Glu efflux similar to that produced by 48 mM ethanol. In the adult, although K+ increased Glu efflux in the presence of CCPA or adenosine, the magnitude of increase was less than that of the K(+)-stimulated Glu efflux for the control conditions. Exposure to ethanol alone or ethanol plus CPT produced a transient increase in endogenous adenosine efflux in the near-term fetal and adult hippocampus, which was not temporally related to the ethanol-induced inhibition of K(+)-stimulated Glu efflux. Overall, the data indicate that adenosine A1 receptor activation mediates ethanol-induced inhibition of stimulated Glu release in the hippocampus of the near-term fetal and adult guinea pig.
Reynolds
J D
JD
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
Brien
J F
JF
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D005333:Fetus / Q000378:metabolism*; D006168:Guinea Pigs; D006624:Hippocampus / Q000196:embryology* / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C053907:8-cyclopentyl-1,3-dimethylxanthine; C058394:2-chloro-N(6)cyclopentyladenosine; D000431:Ethanol; D013806:Theophylline; D000241:Adenosine; D011188:Potassium