Interaction between the carbon monoxide and nitric oxide pathways in the locus coeruleus during fever.

作者: R.N. Soriano , M. Kwiatkoski , M.E. Batalhao , L.G.S. Branco , E.C. Carnio

DOI: 10.1016/J.NEUROSCIENCE.2012.01.021

关键词: ChemistryNitric oxideHeme oxygenaseMicroinjectionAntipyreticPharmacologyLipopolysaccharideBilirubinBiochemistryArginineNitric oxide synthase

摘要: Abstract We have documented that the locus coeruleus (LC), main noradrenergic nucleus in brain, is part of a thermoeffector neuronal pathway fever induced by lipopolysaccharide (LPS). Following this pioneering study, we investigated role LC carbon monoxide (CO) and nitric oxide (NO) pathways fever. Interestingly, despite both CO NO are capable activating same intracellular target, soluble guanylate cyclase (sGC), our data shown an antipyretic molecule, whereas propyretic. Thus, aiming at further exploring mechanisms underlying their anti- propyretic properties, putative interplay between pathways. Male Wistar rats were implanted with guide cannula fourth ventricle (4V) temperature datalogger capsule peritoneal cavity. The animals microinjected into 4V inhibitor heme oxygenase (HO) (ZnDPBG [zinc(II)deuteroporphyrin IX 2,4 bis ethylene glycol]), or donor (CORM-2 [tricarbonyldichlororuthenium-(II)-dimer]), synthase (NOS) (l-NMMA [NG-monomethyl- l -arginine acetate]), (NOC12 [3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene]), injected LPS (100 μg/kg i.p.). Two hours later, decapitated, brains frozen cut cryostat. punches processed to assess bilirubin nitrite/nitrate (NOx) levels. Microinjection ZnDPBG reduced increased NOx, l-NMMA diminished NOx bilirubin. Furthermore, NOC12 caused increase bilirubin, CORM-2 reduction NOx. These findings consistent notion during downmodulates NOS activity upmodulates HO activity, and, together previous data, allow us conjecture blunts downmodulating (antipyretic property), sGC activities favoring development (propyretic effect).

参考文章(88)
A. Friebe, G. Schultz, D. Koesling, Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme. The EMBO Journal. ,vol. 15, pp. 6863- 6868 ,(1996) , 10.1002/J.1460-2075.1996.TB01078.X
Yan Ding, William K. McCoubrey Jr, Mahin D. Maines, Interaction of heme oxygenase‐2 with nitric oxide donors FEBS Journal. ,vol. 264, pp. 854- 861 ,(1999) , 10.1046/J.1432-1327.1999.00677.X
Maria C. Almeida, Alexandre A. Steiner, Norberto C. Coimbra, Luiz G. S. Branco, Thermoeffector neuronal pathways in fever: a study in rats showing a new role of the Locus coeruleus The Journal of Physiology. ,vol. 558, pp. 283- 294 ,(2004) , 10.1113/JPHYSIOL.2004.066654
Raimo Tenhunen, Harvey S. Marver, Rudi Schmid, Microsomal Heme Oxygenase CHARACTERIZATION OF THE ENZYME Journal of Biological Chemistry. ,vol. 244, pp. 6388- 6394 ,(1969) , 10.1016/S0021-9258(18)63477-5
WJ Wilkinson, HC Gadeberg, AWJ Harrison, ND Allen, D Riccardi, PJ Kemp, Carbon monoxide is a rapid modulator of recombinant and native P2X2 ligand‐gated ion channels British Journal of Pharmacology. ,vol. 158, pp. 862- 871 ,(2009) , 10.1111/J.1476-5381.2009.00354.X
B Brüne, V Ullrich, Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Molecular Pharmacology. ,vol. 32, pp. 497- 504 ,(1987)
Stephen Archer, Measurement of nitric oxide in biological models. The FASEB Journal. ,vol. 7, pp. 349- 360 ,(1993) , 10.1096/FASEBJ.7.2.8440411
Alla El-Din El-Husseini, Christopher Bladen, Steven R. Vincent, Molecular Characterization of a Type II Cyclic GMP‐Dependent Protein Kinase Expressed in the Rat Brain Journal of Neurochemistry. ,vol. 64, pp. 2814- 2817 ,(2002) , 10.1046/J.1471-4159.1995.64062814.X