title: Effects of maturation and acute hypoxia on receptor-IP(3) coupling in ovine common carotid arteries.
abstract: Whereas previous studies have established that many mechanisms mediating pharmacomechanical coupling are subject to regulation, evidence of physiological regulation of the coupling efficiency between receptor activation and second-messenger production is scarce. The present studies address the hypothesis that acute hypoxia and maturation can influence the mass of second-messenger production for each activated agonist-bound receptor ("receptor gain"). For this assessment, receptor density and agonist affinity values were used to calculate 5-hydroxytryptamine (5-HT) concentrations that would produce standardized numbers of bound receptors (8.5 fmol/mg protein) in each experimental group and thus minimize effects of age or hypoxia on receptor density or agonist affinity. After 3 min of exposure to these 5-HT concentrations, normoxic magnitudes of contraction were similar (as %potassium maxima) in fetal (50 +/- 14%) and adult (40 +/- 9%) arteries, but hypoxia (PO(2) approximately 9--12 Torr for 30 min) depressed contractile tensions with a significantly different time course and magnitude in fetal (30 +/- 10%) and adult (17 +/- 11%) arteries (P < 0.05). Basal inositol 1,4,5-trisphosphate (IP(3)) values (in pmol/mg protein) were significantly greater in fetal (94 +/- 16) than in adult (44 +/- 6) arteries, and integrated areas above baseline for the IP(3) time courses (in nmol-s/mg protein) were significantly greater in fetal than in adult arteries both in normoxic (14.3 +/- 1.8 vs. 9.1 +/- 1.6) and hypoxic (15.0 +/- 2.1 vs. 8.6 +/- 1.2) conditions (P < 0.05). Hypoxia altered the IP(3) time courses both in the fetus and the adult but had no significant effect on IP(3 )mobilization or receptor gain. These data demonstrate that for the 5-HT(2a) receptor predominant in this preparation, receptor gain can be experimentally determined, is not influenced by acute hypoxia, but is greater in fetal than in adult ovine carotid arteries.
authors.affiliation: Center for Perinatal Biology, Department of Physiology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Angeles
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: R E
authors.initials: RE
authors.lastname: Purdy
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: W J
authors.initials: WJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D000860:Hypoxia / Q000503:physiopathology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000196:embryology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011247:Pregnancy; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012756:Sheep
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D019331:NG-Nitroarginine Methyl Ester