title: Hypoxia-induced differential modulation of adenosinergic and muscarinic receptors in rat heart.
abstract: To better understand the decreased chronotropic response to catecholamines in chronic hypoxia, we compared the inhibitory pathways regulating adenylate cyclase in rats exposed for 30 days to hypobaric hypoxia (380 Torr; HX) with those in control rats (CT) by the analysis of adenosinergic A1-receptors (8-cyclopentyl-1,3-[3H]dipropylxanthine) and muscarinic M2-receptors ([3H]quinuclidinyl benzilate). A1-receptor density was decreased by 46% in sarcolemmal preparations without a change in the affinity for agonist [(R)-phenylisopropyladenosine]. M2-receptor density was increased (HX: 280 +/- 16 fmol/mg, CT: 188 +/- 15 fmol/mg; n = 7; P < 0.001) without a change in dissociation constant. Displacement of [3H]quinuclidinyl benzilate by carbachol indicated significant decreases in the dissociation constants of both superhigh- (HX: 73 +/- 19 nM, CT: 182 +/- 42 nM; P < 0.001) and high-affinity binding sites (HX: 4 +/- 1 microM, CT: 12 +/- 3 microM; P < 0.001). Our data show that chronic hypoxia leads to differential modulation of cardiac receptors with a downregulation of adenosine receptors and increases in muscarinic receptor affinity and density, which may contribute to the blunted responsiveness of the heart to catecholamines.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 2, Faculté de Médecine, Créteil, France.
authors.forename: R
authors.initials: R
authors.lastname: Kacimi
authors.forename: J P
authors.initials: JP
authors.lastname: Richalet
authors.forename: B
authors.initials: B
authors.lastname: Crozatier
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D000860:Hypoxia / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014970:Xanthines / Q000378:metabolism
chemical_list: D011976:Receptors, Muscarinic; D018047:Receptors, Purinergic P1; D014970:Xanthines; D011813:Quinuclidinyl Benzilate; C051360:1,3-dipropyl-8-cyclopentylxanthine