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J Appl Physiol 91: 343-350, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 1, 343-350, July 2001

Adenosine A1 and A2A receptors modulate sleep state and breathing in fetal sheep

Brian J. Koos, Takatsugu Maeda, and Calvin Jan

Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology and the Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1740

This study was designed to determine the adenosine (Ado) receptor subtype that mediates the depressant effects of Ado on fetal breathing and rapid eye movements (REM). In chronically catheterized fetal sheep (>0.8 term), intra-arterial infusion of N6-cyclopentyladenosine (CPA), an Ado A1-receptor agonist, increased the incidence of high-voltage electrocortical (ECoG) activity while virtually abolishing low-voltage activity, REM, and breathing. These effects were blocked by 9-cyclopentyl-1,3-dipropylxanthine (DPCPX), an Ado A1-receptor antagonist. Infusion of DPCPX alone increased breath amplitude but had no significant effect on inspiratory duration, breath interval, incidence of REM, or incidence of low-voltage activity. Ado A2A-receptor blockade with ZM-241385 increased the incidence of low-voltage ECoG activity, REM, and breathing but had no effect on breath amplitude or respiratory cycle. Both DPCPX and ZM-241385 eliminated the inhibitory effects of Ado on REM and breathing. We conclude that 1) Ado A1 receptors tonically inhibit fetal respiratory drive, 2) Ado A2A receptors tonically inhibit REM-like behavioral state, and 3) both Ado A1 and A2A receptors mediate the depressant effects of Ado on REM and breathing.

behavioral state; brain; respiration; rapid eye movements


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