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Center for Perinatal Biology, Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California 92350
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 (PO2 
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 (IP3) 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 IP3 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 IP3 time courses both in the fetus and the
adult but had no significant effect on IP3 mobilization or
receptor gain. These data demonstrate that for the 5-HT2a
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
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