title: Glutamate-induced calcium signals stimulate CO production in piglet astrocytes.
abstract: Glutamate-stimulated, astrocyte-derived carbon monoxide (CO) causes cerebral arteriole dilation by activating smooth muscle cell large-conductance Ca(2+)-activated K(+) channels. Here, we examined the hypothesis that glutamate activates heme oxygenase (HO)-2 and CO production via the intracellular Ca(2+) concentration ([Ca(2+)](i))/Ca(2+)-calmodulin signaling pathway in newborn pig astrocytes. The major findings are: 1) glutamate stimulated Ca(2+) transients and increased steady-state [Ca(2+)](i) in cerebral cortical astrocytes in primary culture, 2) in astrocytes permeabilized with ionomycin, elevation of [Ca(2+)](i) concentration-dependently increased CO production, 3) glutamate did not affect CO production at any [Ca(2+)](i) when the [Ca(2+)](i) was held constant, 4) thapsigargin, a sarco/endoplasmic reticulum Ca(2+)-ATPase blocker, decreased basal CO production and blocked glutamate-induced increases in CO, and 5) calmidazolium, a calmodulin inhibitor, blocked CO production induced by glutamate and by [Ca(2+)](i) elevation. Taken together, our data are consistent with the hypothesis that glutamate elevates [Ca(2+)](i) in astrocytes, leading to Ca(2+)- and calmodulin-dependent HO-2 activation, and CO production.
authors.affiliation: Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xi
authors.forename: Dilyara
authors.initials: D
authors.lastname: Tcheranova
authors.forename: Shyamali
authors.initials: S
authors.lastname: Basuroy
authors.forename: Helena
authors.initials: H
authors.lastname: Parfenova
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Jaggar
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007476:Ionophores; D018698:Glutamic Acid; C031938:calmidazolium; D015759:Ionomycin; D019284:Thapsigargin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases