inositol-1-4-5-trisphosphate and Fetal-Hypoxia

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.

Topics: Animals; Calcium Channels; Carotid Artery, Common; Female; Fetal Hypoxia; Fetus; Gestational Age; Hypoxia; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Male; Muscle Contraction; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Pregnancy; Receptor Cross-Talk; Receptors, Cytoplasmic and Nuclear; Second Messenger Systems; Serotonin; Sheep