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: Chemistry 、 Nitric oxide 、 Heme oxygenase 、 Microinjection 、 Antipyretic 、 Pharmacology 、 Lipopolysaccharide 、 Bilirubin 、 Biochemistry 、 Arginine 、 Nitric 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).