title: Regulation of CO production in cerebral microvessels of newborn pigs.
abstract: Carbon monoxide (CO) is produced from heme by heme oxygenase-2 (HO-2) in cerebral blood vessels. Gas chromatography-mass spectrometry was used on piglet cerebral microvessels to address the hypothesis that CO production is regulated by heme delivery and HO-2 catalytic activity. CO production appears to be substrate limited because heme and its precursor aminolevulinate increase CO production. Ionomycin also increases CO production. However, CO production from exogenous heme was the same in Ca-replete medium, Ca-free medium with ionomycin, and Ca-replete medium with ionomycin. Phorbol myristate acetate increases CO production but does not change the catalytic activity of HO-2. Also, the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine has no effect on the HO-2 catalytic activity. Protein tyrosine kinase inhibition reduces HO-2 catalytic activity. Inhibition of protein tyrosine phosphatases increased HO-2 catalytic activity. Therefore, regulation of CO production by cerebral microvessels can include changing heme availability and HO-2 catalytic activity. HO-2 catalytic activity is stimulated by tyrosine phosphorylation.
authors.affiliation: Department of Physiology, University of Tennessee, Memphis, TN 38163, USA. cleffler@physio1.utmem.edu
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
authors.forename: Liliya
authors.initials: L
authors.lastname: Balabanova
authors.forename: C Dale
authors.initials: CD
authors.lastname: Sullivan
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Wang
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Fedinec
authors.forename: Helena
authors.initials: H
authors.lastname: Parfenova
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D002196:Capillaries / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism*; D002384:Catalysis; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D010766:Phosphorylation; D017319:Photosensitizing Agents / Q000494:pharmacology; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007476:Ionophores; D017319:Photosensitizing Agents; D020032:Tyrphostins; C060152:tyrphostin 47; D014638:Vanadates; D006418:Heme; D015759:Ionomycin; D002248:Carbon Monoxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000622:Aminolevulinic Acid; D019833:Genistein; D006419:Heme Oxygenase (Decyclizing); D013755:Tetradecanoylphorbol Acetate; D002118:Calcium