Abstract
The aim of the present study was to investigate the possibility that endotoxin fever in rats is mediated by arachidonic acid (AA) which in turn is converted to the active metabolites such as prostaglandin (PG) E2, PGF2α, thromboxane A2 (TxA2), or prostacyclin (PGI2). Evidence is presented indicating that PGE2 induces, fever (not hyperthermia) by acting on the anterior hypothalamic preoptic area. Conversely, both PGF2α and AA produce mutually similar hyperthermia and there is no correlation between their microinjection sites in the diencephalon and the observed hyperthermic response. In addition, evidence is presented suggesting that involvement of other metabolites of AA, namely TxA2 and PGI2 in the mediation of endotoxin fever in rats seems unlikely. Only PGE2-induced fever is significantly similar, consistent with the parameters of this study, to endotoxin-induced fever in rats. AA-induced hyperthermia is probably brought about by increased levels of PGF2α or both PGF2α and PGE2 in the hypothalamus following AA injection. It seems highly unlikely that endotoxin produces fever in rats through the mcreased availability of free AA or through the activation of the PG endoperoxide synthetase in the hypothalamus. The mechanism by which endotoxin may increase PGE2 levels in the rat hypothalamus remains unknown.
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Clark, W. G., Cumby, H. R.: Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat. J. Physiol. (Lond.)257, 581–595 (1976)
Cottee, F., Flower, R. J., Salmon, J. A., Vane, J. R.: Synthesis of 6-keto-PGF1α by ram seminal vesicle microsomes. Prostaglandins14, 413–424 (1977)
Cranston, W. I., Duff, G. W., Hellon, R. F., Mitchell D. Townsend, Y.: Evidence that brain prostaglandin synthesis is not essential in fever. J. Physiol. (Lond.)259, 239–249 (1976)
Crawshaw, L. I., Stitt, J. T.: Behavioural and autonomic induction of prostaglandin E1 fever in squirrel monkeys. J. Physiol. (Lond.)244, 197–206 (1975)
Feldberg, W., Saxena, P. N.: Prostaglandins, endotoxin and lipid A on body temperature in rats. J. Physiol. (Lond.)249, 601–615 (1975)
Flower, R. J., Blackwell, G. J.: The importance of phospholipase-A2 in prostaglandin biosynthesis. Biochem. Pharmacol.25, 285–291 (1976)
Flower, R. J., Vane, J. R.: Some pharmacologic and biochemical aspects of prostaglandin biosynthesis and its inhibition. In: Prostaglandin synthetase inhibitors (H. J. Robinson and J. R. Vane, eds.). New York: Raven Press 1974)
Górka, Z., Splawiński, J., Kaluża, J., Suder, E.: Prostaglandins E2 and F2α fever in rats. In: Symposium on prostaglandins (J. Knoll and K. Kelemen, eds.). Budapest: Akademiai Kiado 1976
Gornall, A. G., Bardawill, C. J., David, M. M.: Determination of serum proteins by means of the biuret reaction. J. Biol. Chem.177, 751–766 (1949)
Gryglewski, R.: Prostaglandin and thromboxane biosynthesis inhibitors. Naunyn-Schmiedeberg's Arch. Phamacol.297, S85-S88 (1977)
Gryglewski, R. J., Bunting, S., Moncada, S., Flower, R. F., Vane, J. R.: Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins12, 685–713 (1976)
Gryglewski, R. J., Panczenko, B., Korbut, R., Grodzińska, L., Ocetkiewicz, A.: Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins10, 343–355 (1975)
Hawkins, M., Lipton, J. M.: Analogs of endoperoxide precursors of prostaglandins: failure to affect body temperature when injected into primary and secondary central temperature controls. Prostaglandins13, 209–218 (1977)
Laburn, H., Mitchell, D., Rosendorff, C.: Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits. J. Physiol. (Lond)267, 559–570 (1977)
Marrazzi, M. A., Matschinsky, F. M.: Properties of 15-hydroxy prostaglandin dehydrogenase: structural requirements for substrate binding. Prostaglandins1, 373–388 (1972)
Milton, A. S.: Modern views on the pathogenesis of, fever and the mode of action of antipyretic drugs. J. Pharm. Pharmacol.28, 393–399 (1976)
Pace-Asciak, C. R.: Minireview-oxidative biotransformations of arachidonic acid. Prostaglandins13, 811–817 (1977)
Pace-Asciak, C. R., Rangaraj, G.: Distribution of prostaglandin biosynthetic pathways in several rat tissues, formation of 6-ketoprostaglandin F1α. Biochim. Biophys. Acta486, 579–582 (1977)
Philipp-Dormston, W. K.: Prostaglandins as possible mediators of fever genesis in man. Zbl. Bakt. Hyg., I. Abt. Orig. A236, 415–421 (1976)
Philipp-Dormston, W. K., Siegert, R.: Prostaglandins of the E and F series in rabbit cerebrospinal fluid during fever induced by Neacastle disease virus. E. coli-endotoxin, or endogenous pyrogen. Med. Microbiol. Immunol.159, 279–284 (1974)
Piper, P., Vane, J.: The release of prostaglandins from lung and other tissues. Ann. N. Y. Acad. Sci.180, 363–383 (1971)
Rand, R. P., Burton, A. C., Ing, T.: The tail of the rat in temperature regulation and acclimatization. Can. J. Physiol. Pharmacol.43, 257–267 (1965)
Samuelsson, B.: Introduction: new trends in prostaglandin research. In: Advances in prostaglandin and thromboxane research, vol. 1 (B. Samuelsson and R. Paoletti, eds.). New York: Raven Press 1976
Skinner, J. E.: Neuroscience: a laboratory manual. Philadelphia-London-Toronto: W. B. Saunders Comp. 1971
Splawiński, J. A., Górka, Z., Zacny, E., Kaluża, J.: Fever produced in the rat by intracerebral E. coli endotoxin. Pflügers Arch.368, 117–123 (1977)
Splawiński, J. A., Nies, A. S., Sweetman, B., Oates, J. A.: The effects of arachidonic acid, prostaglandin E2 and prostaglandin F2α on the longitudinal stomach strip of the rat. J. Pharmacol. Exp. Ther.187, 501–510 (1973)
Splawiński, J. A., Reichenberg, K., Vetulani, J., Marchaj, J., Kaluża, J.: Hyperthermic effect of intraventricular injections of arachidonic acid and prostaglandin E2 in the rat. Pol. J. Pharmacol. Pharm.26, 101–107 (1974)
Stitt, J. T.: Prostaglandin E1 fever induced in rabbits. J. Physiol. (Lond.)232, 163–179 (1973)
Veale, W. L., Whishaw, I. Q.: Body temperature responses at different ambient temperatures following injections of prostaglandin E1 and noradrenaline into the brain. Pharmacol. Biochem. Behav.4, 143–150 (1976)
Williams, J. W., Rudy, T. A., Yaksh, T. L., Viswanathan, C. T.: An extensive exploration of the rat brain for sites mediating prostaglandin-induced hyperthermia. Brain Res.120, 251–262 (1977)
Wolfe, L. S., Pappius, H. M., Marion, J.: The biosynthesis of prostaglandins by brain tissue in vitro. In: Advances in prostaglandin and thromboxane research, vol. 1 (B. Samuelsson and R. Paoletti, eds.). New York: Raven Press 1976a
Wolfe, L. S., Rostworowski, K., Marion, J.: Endogenous formation of the prostaglandin endoperoxide metabolite, thromboxane B2, by brain tissue. Biochem. Biophys. Res. Commun.70, 907–913 (1976b)
Ziel, R., Krupp, P.: Influence of endogenous pyrogen on the cerebral prostaglandin-synthetase system. Experientia32, 1451–1453 (1976)
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Splawinski, J.A., Górka, Z., Zacny, E. et al. Hyperthermic effects of arachidonic acid, prostaglandins E2 and F2α in rats. Pflügers Arch. 374, 15–21 (1978). https://doi.org/10.1007/BF00585692
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DOI: https://doi.org/10.1007/BF00585692