Abstract

The objective of this proposal is to determine in the perinatal lung the regulation of metabolism of PAF and to determine the regulation and distribution of PAF receptors. The two specific aim are to 1) determine the regulation of PAF metabolism via its synthesis by acetyltransferase and CDPcholine:CPTrase enzymes and via its catabolism by acetylhydrolase enzyme; and 2) characterize the distribution of PAF receptors and binding of PAF to its receptors in the lung as a function of age. Experiments will be done in lung parenchymal tissue, isolated intrapulmonary arteries and veins, and in endothelial cell cultures from pulmonary arteries and veins of full term fetuses, less than 1 day old lambs, and 6-12 day old lambs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL047804-06A1
Application #
2693327
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1992-08-13
Project End
2002-07-31
Budget Start
1998-09-01
Budget End
1999-07-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
La Biomed Research Institute/ Harbor UCLA Medical Center
Department
Type
DUNS #
City
Torrance
State
CA
Country
United States
Zip Code
90502

  Publications

Ibe, Basil O; Portugal, Ada M; Usha Raj, J (2002) Metabolism of platelet activating factor by intrapulmonary vascular smooth muscle cells. Effect of oxygen on phospholipase A2 protein expression and activities of acetyl-CoA acetyltransferase and cholinephosphotransferase. Mol Genet Metab 77:237-48
Raj, Usha; Shimoda, Larissa (2002) Oxygen-dependent signaling in pulmonary vascular smooth muscle. Am J Physiol Lung Cell Mol Physiol 283:L671-7
Ibe, B O; Raj, J U (2001) Leukotriene metabolism by intrapulmonary vessels of newborn lambs: effect of platelet-activating factor. Exp Lung Res 27:331-48
Ibe, B O; Pham, H H; Kaapa, P et al. (2001) Maturational changes in ovine pulmonary metabolism of platelet-activating factor: implications for postnatal adaptation. Mol Genet Metab 74:385-95
Ibe, B O; Sander, F C; Raj, J U (2000) Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth. Am J Physiol Heart Circ Physiol 278:H1168-76
Ibe, B O; Sander, F C; Raj, J U (2000) Platelet activating factor acetylhydrolase activity in lamb lungs is up-regulated in the immediate newborn period. Mol Genet Metab 69:46-55
Gao, Y; Tolsa, J F; Botello, M et al. (1998) Developmental change in isoproterenol-mediated relaxation of pulmonary veins of fetal and newborn lambs. J Appl Physiol 84:1535-9
Ibe, B O; Hibler, S; Raj, J U (1998) Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb. J Appl Physiol 85:1079-85
Gao, Y; Tolsa, J F; Raj, J U (1998) Heterogeneity in endothelium-derived nitric oxide-mediated relaxation of different sized pulmonary arteries of newborn lambs. Pediatr Res 44:723-9
Gao, Y; Tolsa, J F; Shen, H et al. (1998) Effect of selective phosphodiesterase inhibitors on response of ovine pulmonary arteries to prostaglandin E2. J Appl Physiol 84:13-8

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