Mechanism of glutamate stimulation of CO production in cerebral microvessels.
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.
Leffler
Charles W
CW
Department of Physiology, University of Tennessee, Memphis, TN 38163, USA. cleffler@physio1.utmem.edu
Balabanova
Liliya
L
Fedinec
Alexander L
AL
Waters
Christopher M
CM
Parfenova
Helena
H
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002196:Capillaries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D018698:Glutamic Acid / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013552:Swine
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases