title: Adenosine A(1) and A(2A) receptors modulate sleep state and breathing in fetal sheep.
abstract: 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 N(6)-cyclopentyladenosine (CPA), an Ado A(1)-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 A(1)-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 A(2A)-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 A(1) receptors tonically inhibit fetal respiratory drive, 2) Ado A(2A) receptors tonically inhibit REM-like behavioral state, and 3) both Ado A(1) and A(2A) receptors mediate the depressant effects of Ado on REM and breathing.
authors.affiliation: 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, USA. bkoos@mednet.ucla.edu
authors.forename: B J
authors.initials: BJ
authors.lastname: Koos
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: C
authors.initials: C
authors.lastname: Jan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005333:Fetus / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D012756:Sheep / Q000196:embryology; D012894:Sleep Stages / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine