Preoptic norepinephrine mediates the febrile response of guinea pigs to lipopolysaccharide

Feleder, Carlos; Perlik, Vit; Blatteis, Clark M.

doi:10.1152/ajpregu.00067.2007

Cited by 35 publications

(47 citation statements)

References 68 publications

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“…The novel finding that Cirazoline induced a rapid-onset hyperthermia independent of PGE 2 production suggested that alpha-1 ARs have an important role in the early development of a febrile response (Feleder et al, 2007). Antagonism of the alpha-1 ARs adds support for this observation, ultimately hindering rapid onset of fever and reducing its high point (Feleder, 2004).…”

Section: Discussionmentioning

confidence: 97%

“…This early hyperthermia likely attenuates due to eventual desensitization at the postsynaptic alpha-1 ARs, the induction of COX-2 expression by activation of alpha-2 ARs, ensuing PGE 2 synthesis, and action at Prostaglandin E receptors (EP; presumably the EP 3 subtype) which contribute the late phase of fever (Feleder et al, 2007;Lazarus et al, 2007;Oka, 2004). The application of norepinephrine in the POAH has been shown to increase the frequency of spontaneous, miniature inhibitory postsynaptic currents (IPSCs) via the alpha-1 AR, and likewise decrease the frequency of IPSCs via the alpha-2 AR (Kolaj and Renaud, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Upon arrival in the liver, LPS is taken up by Kupffer cells (Kc) and a complement cascade is activated, promoting Kc to release PGE 2 and stimulate hepatic vagal afferents that project to the POAH (Li et al, 2006). It is then the release of norepinephrine via the hepatic vagus which mediates this response to peripheral LPS (Feleder et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

et al. 2008

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Peripheral exposure to LPS induces a biphasic fever thought to be initiated via vagal afferents to the preoptic area of the anterior hypothalamus (POAH), an important thermoregulatory control center in the brain. Previous studies have shown norepinephrine synaptically mediates this Prostaglandin E 2 (PGE 2 )-dependent change in temperature through the selective activation of alpha-2 adrenoreceptors (AR). However, there is clear evidence that alpha-1 AR activation of thermoregulatory hypothalamic neurons will result in a rapid hyperthermia that is not dependent on PGE 2 . This direct action of norepinephrine in the POAH was tested in the present study by recording the single-unit activity of POAH neurons in a tissue slice preparation from the adult male rat, in response to temperature and the selective alpha-1 AR agonist Cirazoline (1−100 μM). Neurons were classified as either warm sensitive or temperature insensitive. Warm sensitive neurons responded to Cirazoline with a decrease in firing rate, while temperature insensitive neurons showed a firing rate increase. These responses are similar to those reported for PGE 2 and suggest that both warm sensitive and temperature insensitive neurons in the POAH are important in mediating this alpha-1 AR dependent hyperthermic shift in body temperature.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

et al. 2008

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“…However, how norepinephrine acts on the febrile local mechanism in the POA is unknown. Although adrenoreceptor agonists and antagonists have been applied into the POA to examine their effects on LPS-or PGE 2 -induced fever, inconsistent results have been obtained (37,128). Noradrenergic inputs to the POA are likely provided by A1, A2, and locus coeruleus neurons in the pons and the medulla oblongata (184).…”

Section: Central Processing Of Pyrogenic Signals For Fever Developmentmentioning

confidence: 99%

Central circuitries for body temperature regulation and fever

Nakamura

2011

American Journal of Physiology-Regulatory, Integrative and Comp

432

394

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Nakamura K. Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol 301: R1207-R1228, 2011. First published September 7, 2011 doi:10.1152/ajpregu.00109.2011.-Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E 2 produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.

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“…These findings therefore indicated that NO could, in turn, modulate monoaminergic neurotransmission in the central nervous system. Evidence for the putative involvement of NE and ␣ 1 -AR in the initiation of fever was presented in our companion paper (15). Hence the existence of a mutually antagonistic NE-NO interaction in the POA in response to intravenous LPS is plausible.…”

mentioning

confidence: 90%

Preoptic nitric oxide attenuates endotoxic fever in guinea pigs by inhibiting the POA release of norepinephrine

Feleder¹,

Perlik²,

Blatteis³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Lipopolysaccharide (LPS) administration induces hypothalamic nitric oxide (NO); NO is antipyretic in the preoptic area (POA), but its mechanism of action is uncertain. LPS also stimulates the release of preoptic norepinephrine (NE), which mediates fever onset. Because NE upregulates NO synthases and NO induces cyclooxygenase (COX)-2-dependent PGE2, we investigated whether NO mediates the production of this central fever mediator. Conscious guinea pigs with intra-POA microdialysis probes received LPS intravenously (2 μg/kg) and, thereafter, an NO donor (SIN-1) or scavenger (carboxy-PTIO) intra-POA (20 μg/μl each, 2 μl/min, 6 h). Core temperature (Tc) was monitored constantly; dialysate NE and PGE2 were analyzed in 30-min collections. To verify the reported involvement of α2-adrenoceptors (AR) in PGE2 production, clonidine (α2-AR agonist, 2 μg/μl) was microdialyzed with and without SIN-1 or carboxy-PTIO. To assess the possible involvement of oxidative NE and/or NO products in the demonstrated initially COX-2-independent POA PGE2 increase, (+)-catechin (an antioxidant, 3 μg/μl) was microdialyzed, and POA PGE2, and Tc were determined. SIN-1 and carboxy-PTIO reduced and enhanced, respectively, the rises in NE, PGE2, and Tc produced by intravenous LPS. Similarly, they prevented and increased, respectively, the delayed elevations of PGE2 and Tc induced by intra-POA clonidine. (+)-Catechin prevented the LPS-induced elevation of PGE2, but not of Tc. We conclude that the antipyretic activity of NO derives from its inhibitory modulation of the LPS-induced release of POA NE. These data also implicate free radicals in POA PGE2 production and raise questions about its role as a central LPS fever mediator.

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Preoptic norepinephrine mediates the febrile response of guinea pigs to lipopolysaccharide

Cited by 35 publications

References 68 publications

The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

Central circuitries for body temperature regulation and fever

Preoptic nitric oxide attenuates endotoxic fever in guinea pigs by inhibiting the POA release of norepinephrine

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