PMID- 1933275 OWN - NLM STAT- MEDLINE DCOM- 19911224 LR - 20190613 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 553 IP - 1 DP - 1991 Jul 5 TI - Leukotrienes in brain: natural occurrence and induced changes. PG - 4-13 AB - Peptidoleukotrienes (SP-LTs) (both total product and individual LTC4 and LTE4 and LTB4 were measured by radioimmunoassay in cerebrospinal fluid (CSF) collected from the third ventricle of conscious cats. Total SP-LT was expressed as LTE4 after treating samples with crude gamma-glutamyltranspeptidase. Prostaglandin (PG) E2 and thromboxane (TX) B2, the stable metabolite of TXA2, were also assayed in part of the experiments. Under basal conditions, SP-LT and LTC4 were consistently measurable (respectively, 327 +/- 14 and 244 +/- 41 pg/ml), while native LTE4 was below the threshold of the assay (60-280 pg/ml) in most cases. LTB4 was barely detectable (30 +/- 2 pg/ml) or not detectable at all. PGE2 was normally less abundant than TXB2 (31 +/- 4 vs 281 +/- 47 pg/ml). Intracerebroventricular (i.c.v.) administration of arachidonic acid (40 microgram) caused a 4-fold increase in SP-LT levels which was relatively small and transient compared to PGE2 (76-fold) and TXB2 (23-fold), while there was no change in either native LTE4 or LTB4. A similar response was obtained with platelet-activating factor (PAF, 1 microgram i.c.v.), though SP-LT elevation (4-fold) was more persistent. A further rise in SP-LT (9-fold) was noted when PAF administration was preceded by indomethacin (500 microgram i.c.v.), whereas PAF effect was reversed by pretreatment with either the PAF antagonist, BN52021 (1 microgram i.c.v.), or the 5-lipoxygenase inhibitors, U-60,257 (75 micrograms i.c.v.) and L-651,392 (10 mg/kg p.o.). PAF was also effective in causing a 3-fold rise in LTC4. Unlike PAF, pyrogens (endotoxin i.c.v. or i.v.; interleukin-1 i.v.) at doses above threshold for fever had no effect on LT levels in CSF, both in the absence and presence of indomethacin pretreatment. We conclude that SP-LTs are a normal constituent of CSF, LTC4, being the major species. The response to PAF accords with a pathogenetic role of the compounds in inflammatory processes and the reactive changes to injury. No evidence was obtained for the involvement of SP-LTs in the central mechanism of fever. FAU - Hynes, N AU - Hynes N AD - Research Institute, Hospital for Sick Children, Toronto, Ont, Canada. FAU - Bishai, I AU - Bishai I FAU - Lees, J AU - Lees J FAU - Coceani, F AU - Coceani F LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Cerebrospinal Fluid Proteins) RN - 0 (Cyclooxygenase Inhibitors) RN - 0 (Leukotrienes) RN - 0 (Lipoxygenase Inhibitors) RN - 0 (Platelet Activating Factor) RN - 0 (Pyrogens) RN - 27YG812J1I (Arachidonic Acid) RN - 54397-85-2 (Thromboxane B2) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Administration, Oral MH - Animals MH - Arachidonic Acid/administration & dosage/pharmacology MH - Body Temperature/drug effects MH - Brain Chemistry/drug effects/*physiology MH - Cats MH - Cerebrospinal Fluid/cytology MH - Cerebrospinal Fluid Proteins/metabolism MH - Cyclooxygenase Inhibitors/pharmacology MH - Dinoprostone/metabolism MH - Female MH - In Vitro Techniques MH - Injections, Intraventricular MH - Leukotrienes/cerebrospinal fluid/*metabolism MH - Lipoxygenase Inhibitors/administration & dosage/pharmacology MH - Male MH - Platelet Activating Factor/administration & dosage/pharmacology MH - Pyrogens/pharmacology MH - Radioimmunoassay MH - Thromboxane B2/metabolism EDAT- 1991/07/05 00:00 MHDA- 1991/07/05 00:01 CRDT- 1991/07/05 00:00 PHST- 1991/07/05 00:00 [pubmed] PHST- 1991/07/05 00:01 [medline] PHST- 1991/07/05 00:00 [entrez] AID - 0006-8993(91)90222-H [pii] AID - 10.1016/0006-8993(91)90222-h [doi] PST - ppublish SO - Brain Res. 1991 Jul 5;553(1):4-13. doi: 10.1016/0006-8993(91)90222-h.