Abstract

The regulation of cyclic nucleotide formation and action in lung and some of its cell types including tracheal smooth muscle will be examined. The accumulation of cyclic GMP and cyclic AMP in tracheal smooth muscle induced with various hormones, neurohormones, nitroso compounds and other materials will be correlated with muscle motility and endogenous protein phosphorylation. Exogenous and endogenous protein substrates for cyclic nucleotide dependent protein kinases in lung and tracheal smooth muscle will be examined. Guanylate cyclase in lung will be characterized, purified and used to obtain antibodies that will be used to develop a radioimmunoassay for the enzyme and immunohistochemical localization of the enzyme in lung. Thus, experiments will be performed with lung and some of its cell types to determine which agents regulate the accumulation and action of cyclic nucleotides in an attempt to ascribe some functions to cyclic AMP and cyclic GMP in lung.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028474-09
Application #
3339863
Study Section
Biochemistry Study Section (BIO)
Project Start
1989-06-06
Project End
1992-05-31
Budget Start
1990-06-06
Budget End
1991-05-31
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Abbott Laboratories
Department
Type
DUNS #
City
North Chicago
State
IL
Country
United States
Zip Code
60064

  Publications

Sheng, H; Ishii, K; Forstermann, U et al. (1995) Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth muscle. Lung 173:373-83
Nakane, M; Schmidt, H H; Pollock, J S et al. (1993) Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett 316:175-80
Pollock, J S; Nakane, M; Buttery, L D et al. (1993) Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies. Am J Physiol 265:C1379-87
Sheng, H; Gagne, G D; Matsumoto, T et al. (1993) Nitric oxide synthase in bovine superior cervical ganglion. J Neurochem 61:1120-6
Schmidt, H H; Gagne, G D; Nakane, M et al. (1992) Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem 40:1439-56
Pollock, J S; Klinghofer, V; Forstermann, U et al. (1992) Endothelial nitric oxide synthase is myristylated. FEBS Lett 309:402-4
Mitchell, J A; Kohlhaas, K L; Matsumoto, T et al. (1992) Induction of NADPH-dependent diaphorase and nitric oxide synthase activity in aortic smooth muscle and cultured macrophages. Mol Pharmacol 41:1163-8
Warner, T D; Budzik, G P; Matsumoto, T et al. (1992) Regional differences in endothelin converting enzyme activity in rat brain: inhibition by phosphoramidon and EDTA. Br J Pharmacol 106:948-52
Klabunde, R E; Kimber, N D; Kuk, J E et al. (1992) NG-methyl-L-arginine decreases contractility, cGMP and cAMP in isoproterenol-stimulated rat hearts in vitro. Eur J Pharmacol 223:1-7
Schmidt, H H; Warner, T D; Nakane, M et al. (1992) Regulation and subcellular location of nitrogen oxide synthases in RAW264.7 macrophages. Mol Pharmacol 41:615-24

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