Effects of maturation and acute hypoxia on receptor-[IP.sub.3] coupling in ovine common carotid arteries

Effects of maturation and acute hypoxia on receptor-[IP.sub.3] coupling in ovine common carotid arteries. Am J Physiol Regulatory Integrative Comp Physiol 280: R410-R417, 2001.--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 [+ or -] 14%) and adult (40 [+ or -] 9%) arteries, but hypoxia ([PO.sub.2] [approximately equals] 9-12 Torr for 30 min) depressed contractile tensions with a significantly different time course and magnitude in fetal (30 [+ or -] 10%) and adult (17 [+ or -] 11/%) arteries (P [is less than] 0.05). Basal inositol 1,4,5-trisphosphate ([IP.sub.3]) values (in pmol/mg protein) were significantly greater in fetal (94 [+ or -] 16) than in adult (44 [+ or -] 6) arteries, and integrated areas above baseline for the [IP.sub.3] time courses (in nmol-s/mg protein) were significantly greater in fetal than in adult arteries both in normoxic (14.3 [+ or -] 1.8 vs. 9.1 [+ or -] 1.6) and hypoxic (15.0 [+ or -] 2.1 vs. 8.6 [+ or -] 1.2) conditions (P [is less than] 0.05). Hypoxia altered the [IP.sub.3] time courses both in the fetus and the adult but had no significant effect on [IP.sub.3] mobilization or receptor gain. These data demonstrate that for the 5-[HT.sub.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. serotonin; intrinsic efficacy; coupling efficiency; fetal lamb; grams protein