Hyperthermic effects of arachidonic acid, prostaglandins E2 and F2? in rats

Spławiński, Jacek; Górka, Z; Zacny, Elżbieta; Wojtaszek, B.

doi:10.1007/bf00585692

Cited by 35 publications

(9 citation statements)

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“…The remainder might correspond to active and rapid transport/ binding of PGE 2 in ependymal cells and/or brain parenchymal cells. This notion is supported by an earlier finding that intracerebroventricularly administered PGE 2 induces fever by acting on the anterior hypothalamic pre-optic area (Splawinski et al 1978). The inhibition profiles of PGB 1 , diclofenac, bromocresolgreen, and PAH on [ 3 H]PGE 2 uptake by the isolated choroid plexus were almost identical to those of OAT3-mediated [ 3 H]PGE 2 uptake (Tables 1 and 2).…”

Section: Discussionsupporting

confidence: 77%

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Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E₂ produced in the brain

Tachikawa

Ozeki

Higuchi

et al. 2012

Journal of Neurochemistry

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An increasing level of prostaglandin (PG) E 2 is involved in the progression of neuroinflammation induced by ischemia and bacterial infection. Although an imbalance in the rates of production and clearance of PGE 2 under these pathological conditions appears to affect the concentration of PGE 2 in the cerebrospinal fluid (CSF), the regulatory system remains incompletely understood. The purpose of this study was to investigate the cellular system of PGE 2 production via microsomal PGE synthetase-1 (mPGES-1), the inducible PGE 2 -generating enzyme, and PGE 2 elimination from the CSF via the blood-CSF barrier (BCSFB). Immunohistochemical analysis revealed that mPGES-1 was expressed in the soma and perivascular sheets of astrocytes, pia mater, and brain blood vessel endothelial cells, suggesting that these cells are local production sites of PGE 2 in the CSF. The in vivo PGE 2 elimination clearance from the CSF was eightfold greater than that of D-mannitol, which is considered to reflect CSF bulk flow. This process was inhibited by the simultaneous injection of unlabeled PGE 2 and b-lactam antibiotics, such as benzylpenicillin, cefazolin, and ceftriaxone, which are substrates and/or inhibitors of organic anion transporter 3 (OAT3). The characteristics of PGE 2 uptake by the isolated choroid plexus were at least partially consistent with those of OAT3. OAT3 was able to mediate PGE 2 transport with a Michaelis-Menten constant of 4.24 lM. These findings indicate that a system regulating the PGE 2 level in the CSF involves OAT3-mediated PGE 2 uptake by choroid plexus epithelial cells, acting as a cerebral clearance pathway via the BCSFB of locally produced PGE 2 . Keywords: blood-cerebrospinal fluid barrier, clearance, inflammation, mPGES-1, prostaglandin E 2 , prostaglandin synthase. J. Neurochem. (2012) 123, 750-760. Prostaglandin (PG) E 2 is the crucial mediator, which propagates neuroinflammation induced by ischemia and bacterial infection. The PGE 2 level is significantly increased in the Cerebrospinal fluid (CSF) of the patients suffering from stroke (0.57-8.5 nM;Carasso et al. 1977) and lipopolysaccharide (LPS)-treated rats (~3.4 nM; Gao et al. 2009), although the PGE 2 concentration in normal CSF is below the detection limit in humans (Romero et al. 1984) and 0.15 nM in rats (Gao et al. 2009). As a positive correlation has been found between the PGE 2 level in the CSF and the severity and clinical outcome of the stroke (Carasso et al. 1977), the CSF concentration of PGE 2 appears to be a key determinant of the progression of neuroinflammation.Received June 12, 2012; revised manuscript received August 29, 2012; accepted September 08, 2012.Address correspondence and reprint requests to Ken-ichi Hosoya, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. E-mail: hosoyak@pha.u-toyama.ac.jp Abbreviations used: BBB, blood-brain barrier; BCSFB, bloodcerebrospinal fluid barrier; CHO, Chinese hamster ovary; cPGES, cytosolic prostaglandin E synthetase; CSF, cer...

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Section: Discussionsupporting

confidence: 77%

“…This notion is supported by an earlier finding that intracerebroventricularly administered PGE 2 induces fever by acting on the anterior hypothalamic pre‐optic area (Splawinski et al . ).…”

Section: Discussionmentioning

confidence: 97%

Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E₂ produced in the brain

Tachikawa

Ozeki

Higuchi

et al. 2012

Journal of Neurochemistry

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“…We also injected a low dose of indomethacin by this route and found it ineffective in attenuating the effects of sodium arachidonate (unpublished observations). Splawinski et al (1974) were, however, able to reduce the pyrogenic effects of sodium arachidonate in rats after pretreatment with aspirin.…”

Section: Arachidonate Fevermentioning

confidence: 99%

Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits.

Laburn¹,

Mitchell²,

Rosendorff³

1977

The Journal of Physiology

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SUMMARY1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration.2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546.3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1.4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic.

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“…The highest activity of the PGD synthetase in the rat brain has been fOtmd in the hypothalanrus and thalamus (6), the brain areas important for cardiovascular (7) and thermal (3, 8) homeostasis. Prostaglandins of the E-type are known to be highly active hyperthermic agents in the brain (8,9). In additi?n, central administration of PGE2 or PGF~ induce strong dose-related Increases in blood pressure, heart rate and body temperature of the urethaneanaesthetised rat (1,4).…”

Section: Introductionmentioning

confidence: 99%

Central cardiovascular and thermal effects of prostaglandin D2 in rats

Sirén

1982

Prostaglandins, Leukotrienes and Medicine

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Prostaglandin Dz (PGD z ) is the most common prostaglandin type of tile rat brain. Recently a neurornodulator role for PGD z has been suggested. In the present work the central cardiovascular and thermal effects of PGDz were studied in urethane-anaesthetised rats. Mlen adrndnistered at the doses of 0.001-10 ~g/rat into the lateral cerebral ventricle(i.c.v.), PGD2 slightly increased the blood pressure, heart rate and body ternperaure.The highest dose caused also an initial hypotensive effect. Upon lntravenous injections PGD2 (0.1-10 ~g/rat) initially decreased and then weakly increased the blood pressure but had only negligible effects on heart rate and body temperature. Central pretreatment with sodium meclofenamate or indomethacin (1 mg/rat i.c.v.) antagonised effectively all the recorded central effects of PGD2.The central cardiovascular and thermal effects of PGD 2 were much weaker than those obtained earlier with other prostaglandins, such as PGF2a. and PGE2.. Therefore, in spite of its ablUldance in the brain PGD 2 may not be very important for the central cardiovascular and thermal regulation in the rat.

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Hyperthermic effects of arachidonic acid, prostaglandins E2 and F2? in rats

Cited by 35 publications

References 26 publications

Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E₂ produced in the brain

Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E₂ produced in the brain

Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits.

Central cardiovascular and thermal effects of prostaglandin D2 in rats

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Hyperthermic effects of arachidonic acid, prostaglandins E2 and F2? in rats

Cited by 35 publications

References 26 publications

Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E2 produced in the brain

Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E2 produced in the brain

Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits.

Central cardiovascular and thermal effects of prostaglandin D2 in rats

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Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E₂ produced in the brain

Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E₂ produced in the brain