Abstract
The present work examined some central nervous actions of prostaglandin D2 (PGD2), which is the most prevalent prostaglandin in rodentorain. The effects of PGD2 were compared with those of PGE2 and PGF2α. The prostaglandins were administered intracerebroventricularly (ICV) to conscious rats using the method of Herman (1970). All three prostaglandins studied produced depressive behavioral effects, causing obvious sedation at doses of 2.0 μg and 20.0 μg ICV. PGD2 and PGE2 significantly reduced spontaneous motor activity at doses of 2.0 μg and 20.0 μg ICV. PGF2α was less effective; only 20.0 μg significantly inhibited motor activity. At a dose of 20.0 μg ICV all three compounds were shown to block convulsions induced by pentylenetetrazol. PGD2, the most effective prostaglandin in this respect, was still slightly anticonvulsive at a dose of 2.0 μg ICV. PGF2α hat the weakest anticonvulsive potency. PGE2 and PGF2α (2.0 μg and 20.0 μg ICV) caused a marked hypertensive effect, whereas PGD2 at the same dose levels only produced a small increase in blood pressure. PGE2 and PGF2α (2.0 μg and 20.0 μg) also exerted marked pyrogenic actions. The effects of PGD2 on body temperature were variable. When given at a dose of 20.0 μg ICV, it caused slight hyperthermia whereas a lower dose (2.0 μg ICV) induced a moderate fall in body temperature. These findings suggest a relationship between the actions of the different prostaglandins on blood pressure and body temperature.
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References
Abdel-Halim MS, Hamberg M, Sjöquist B, Änggård E (1977) Identification of prostaglandin D2 as the major prostaglandin in homogenates of rat brain. Prostaglandins 14:633–643
Abdel-Halim MS, Änggård E (1979) Regional and species differences in endogenous prostaglandin biosynthesis by brain homogenates. Prostaglandins 17:411–418
Anhut H, Peskar BA, Wachter W, Gräbling B, Peskar BM (1978) Radioimmunological determination of prostaglandin D2 synthesis in human thrombocytes. Experientia 34:1494–1496
Baxter CE, Patrick GA, Harris LS (1980) The depressant action of prostaglandin D2 and interactions with serotoninergic modulators. Pharmacologist 22:183
Berchtold-Kanz E, Anhut H, Heldt R, Neufang B, Hertting G (1981) Regional distribution of arachidonic acid metabolites in rat brain following convulsive stimuli. Prostaglandins 22:67–79
Bhattacharya SK, Sanyal AK (1978) Inhibition of pentylenetetrazol-induced convulsions in rats by prostaglandin E1: Role of brain monoamines. Psychopharmacology 56:235–237
Bosisio E, Galli C, Galli G, Nicosia S, Spagnuolo C, Tosi L (1976) Correlation between release of free arachidonic acid and prostaglandins formation in brain cortex and cerebellum. Prostaglandins 11:776–781
Brus R, Herman ZS, Szkilnik R, Zabawska J (1979) Mediation of central prostaglandin effects by serotoninergic neurons. Psychopharmacology 64:113–120
Ellis CK, Smigel MD, Oates JA, Oelz O, Sweetman BJ (1979) Metabolism of prostaglandin D2 in the monkey. J Biol Chem 254:4152–4163
Ewen L, Milton AS, Smith S (1976) Effects of prostaglandin F2α and prostaglandin D2 on body temperature of conscious cats. J Physiol (Lond) 258:121P-122P
Feldberg W, Milton AS (1978) Prostaglandins and body temperature. In: Vane JR, Ferreira SH (eds) Handbook of experimental pharmacology, vol 50. I. Springer, Berlin Heidelberg New York, pp 615–656
Ferreira SH, Vane JR (1967) Their disappearance from and release into the circulation. Nature 216:868–873
Feuerstein G, Helke CJ, Zerpe RL, Jacobowitz DM, Kopin IJ (1982) Mechanisms involved in the central cardiovascular effects of prostaglandin F2α. Am J Physiol 242:R545-R551
Förstermann U, Heldt R, Knappen F, Hertting G (1982) Potential anticonvulsive properties of prostaglandins formed in mouse brain. Brain Res 240:303–310
Förstermann U, Heldt R (1983) Central actions of prostaglandins D2, E2 and F2α in the rat. Naunyn-Schmiedeberg's Arch Pharmacol (Suppl) 322:R88
Galli C, Spagnuolo C, Petroni A (1980) Factors affecting brain prostaglandin formation. In: Samuelsson B, Paoletti R (eds) Advances in prostaglandin and thromboxane research. Raven, New York, pp 1235–1239
Gaudet RJ, Alam I, Levine L (1980) Accumulaltion of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion. J Neurochem 35:653–658
Hansson E, Samulsson B (1965) Autoradiographic distribution studies of 3H-labeled prostaglandin E1 in mice. Biochim Biophys Acta 106:379–385
Herman ZS (1970) The effect of noradrenaline on rat's behaviour. Psychopharmacologia 16:369–374
Herman ZS, Kmieciak-Kolada K, Wolny HL, Slominska-Zurek J, Bonczek A (1976) Central effects of prostaglandin F2α and E1. Pol J Pharmacol Pharm 28:411–421
Holmes SW, Horton EW (1968) Prostaglandins and the central nervous system. In: Ramwell PW, Shaw JE (eds) Prostaglandin symposium of the Worcester Foundation for Experimental Biology. Interscience, New York, pp 21–38
Horton EW (1964) Actions of prostaglandins E1, E2 and E3 on the central nervous system. Br J Pharmacol 22:189–192
Horton EW, Main IHM (1965) Differences in the effects of prostaglandin F2α a constituent of cerebral tissue, and prostaglandin E1 on conscious cats and chicks. Int J Neuropharmacol 4:65–69
Laychock SG, Johnson DN, Harris LS (1980) PGD2 effects on rodent behaviour and EEG pattern in cats. Pharmacol Biochem Behav 12:747–754
Lipton JM (1980) Fever. Raven, New York
Marion J, Wolfe LC (1978) Formation in vivo of unesterified fatty acids, prostaglandin F2α but not thromboxane B2 in rat brain during drug induced convulsions. Prostaglandins 16:99–109
Milton AS, Wendlandt S (1970) A possible role for prostaglandin E1 as a modulator of temperature regulation in the central nervous system of the cat. J Physiol (Lond) 207:76P-77P
Piper PJ, Vane JR, Wyllie JH (1970) Inactivation of prostaglandins by the lungs. Nature 225:600–604
Poddubiuk ZM (1976) A comparison of the central actions of prostaglandins A1, E1, E2, F1α, and F2α in the rat. Psychopharmacology 50:89–94
Quesney LF, Gloor P, Wolfe LS, Jozsef S (1975) Effect of PGF2α and 15(S)-15-methyl PGE2 methylester on feline generalized penicilin epilepsy. Prostaglandins 10:383–393
Rinchuse DJ, Deuben RR (1976) Central mediated pressor effect by prostaglandins in the rat. Prostaglandins 11:523–530
Rosenkranz RP (1978) Effects of intracerebroventricular administration of PGE1, and E2 and F2α on electrically induced convulsions in mice. Prostaglandins 15:925–942
Rosenkranz RP, Killam KF (1979) Effects of intracerebroventricular administration of prostaglandin E1 and E2 on chemically induced convulsions in mice. J Pharmacol Exp Ther 209:231–237
Steinhauer HB, Anhut H, Hertting G (1979) On the synthesis of prostaglandins and thromboxane in mouse brain in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 310:53–58
Steinhauer HB, Hertting G (1981) Lowering the convulsive threshold by non-steroidal anti-inflammatory drugs. Eur J Pharmacol 69:199–203
Sun FF, Chapman JP, McGuire JC (977) Metabolism of prostaglandin endoperoxides in animal tissue. Prostaglandins 14:1055–1074
Svensson TH, Thieme G (1969) An investigation of a new instrument to measure motor activity of small animals. Psychopharmacologia 14:157–163
Ueno R, Narumiya S, Ogorochi T, Nakayama T, Ishikawa Y, Hayaishi O (1982) Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide. Proc Natl Acad Sci USA 79:6093–6097
Wolfe LS, Coceani F (1979) The role of prostaglandins in the central nervous system. Annu Rev Physiol 41:669–684
Wolfe LS (1982) Eicosanoids: Prostaglandins, thromboxanes, leucotrienes, and other derivatives of carbon-20 unsaturated fatty acids. J Neurochem 38:1–14
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A preliminary report was given at the Spring Meeting of the Deutsche Pharmakologische Gesellschaft, March 1983 (Förstermann and Heldt, 1983)
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Förstermann, U., Heldt, R. & Hertting, G. Effects of intracerebroventricular administration of prostaglandin D2 on behaviour, blood pressure and body temperature as compared to prostaglandins E2 and F2α . Psychopharmacology 80, 365–370 (1983). https://doi.org/10.1007/BF00432122
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DOI: https://doi.org/10.1007/BF00432122