Mechanism of glutamate stimulation of CO production in cerebral microvessels

Charles Leffler, Liliya Balabanova, Alexander L. Fedinec, Christopher M. Waters, Elena Parfenova

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30 Citations (Scopus)

Abstract

Dilation of piglet pial arterioles to glutamate involves carbon monoxide (CO) produced from heme by heme oxygenase-2 (HO-2). Piglet cerebral microvessels and endothelial and smooth muscle cells grown on microcarrier beads were used to address the hypothesis that glutamate increases endothelial CO production by increasing HO-2 catalytic activity. CO was measured by gas chromatography/mass spectrometry. Glutamate increased CO production from endogenous heme by cerebral microvessels, endothelial cells, and smooth muscle cells. Glutamate increased the conversion of exogenous heme to CO. Protein tyrosine kinase inhibition blocked glutamate stimulation of CO production. Inhibition of protein tyrosine phosphatases stimulated CO production. Conversely, neither phorbol myristate acetate nor H-7 changed glutamate stimulation of CO production. The mechanism of HO-2 stimulation by glutamate appears to be independent of cytosolic Ca, because stimulation of CO production by glutamate was the same in Careplete medium, Ca-free medium with ionomycin, and Careplete medium with ionomycin. Therefore, glutamate appears to increase HO-2 catalytic activity in cerebral microvessels via a tyrosine kinase mediated pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number1 54-1
StatePublished - Jul 1 2003

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Carbon Monoxide
Microvessels
Glutamic Acid
Heme
Ionomycin
Protein-Tyrosine Kinases
Smooth Muscle Myocytes
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Protein Tyrosine Phosphatases
Arterioles
Tetradecanoylphorbol Acetate
Gas Chromatography-Mass Spectrometry
Dilatation
Endothelial Cells
heme oxygenase-2

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Mechanism of glutamate stimulation of CO production in cerebral microvessels. / Leffler, Charles; Balabanova, Liliya; Fedinec, Alexander L.; Waters, Christopher M.; Parfenova, Elena.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 1 54-1, 01.07.2003.

Research output: Contribution to journalArticle

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