title: Preoptic norepinephrine mediates the febrile response of guinea pigs to lipopolysaccharide.
abstract: Norepinephrine (NE) microdialyzed in the preoptic area (POA) raises core temperature (T(c)) via 1) alpha(1)-adrenoceptors (AR), quickly and independently of POA PGE(2), and 2) alpha(2)-AR, after a delay and PGE(2) dependently. Since systemic lipopolysaccharide (LPS) activates the central noradrenergic system, we investigated whether preoptic NE mediates LPS fever. We injected LPS (2 microg/kg iv) in guinea pigs prepared with intra-POA microdialysis probes and determined POA cerebrospinal (CSF) NE levels. We similarly microdialyzed prazosin (alpha(1) blocker, 1 microg/microl), yohimbine (alpha(2) blocker, 1 microg/microl), SC-560 [cyclooxygenase (COX)-1 blocker, 5 microg/microl], acetaminophen (presumptive COX-1v blocker, 5 microg/microl), or MK-0663 (COX-2 blocker, 0.5 microg/microl) in other animals before intravenous LPS and measured CSF PGE(2). All of the agents were perfused at 2 microg/min for 6 h. T(c) was monitored constantly. POA NE peaked within 30 min after LPS and then returned to baseline over the next 90 min. T(c) increased within 12 min to a first peak at approximately 60 min and to a second at approximately 150 min and then declined over the following 2.5 h. POA PGE(2) followed a concurrent course. Prazosin pretreatment eliminated the first T(c) rise but not the second; PGE(2) rose normally. Yohimbine pretreatment did not affect the first T(c) rise, which continued unchanged for 6 h; the second rise, however, was absent, and PGE(2) levels did not increase. SC-560 and acetaminophen did not alter the LPS-induced PGE(2) and T(c) rises; MK-0663 prevented both the late PGE(2) and T(c) rises. These results confirm that POA NE is pivotal in the development of LPS fever.
authors.affiliation: Department of Physiology, College of Medicine, University of Tennessee Health Science Center, 894 Union Avenue, Memphis, TN 38163, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Feleder
authors.forename: Vit
authors.initials: V
authors.lastname: Perlik
authors.forename: Clark M
authors.initials: CM
authors.lastname: Blatteis
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002404:Catheterization; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology*; D006168:Guinea Pigs; D007601:Jugular Veins / Q000502:physiology; D008070:Lipopolysaccharides; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011301:Preoptic Area / Q000502:physiology*; D012477:Salmonella enteritidis / Q000737:chemistry; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D015016:Yohimbine; D000082:Acetaminophen; D015232:Dinoprostone; D009638:Norepinephrine; D011224:Prazosin