Prostaglandin profiles in nervous tissue and blood vessels of the brain of various animals.

The endogenous formation of prostaglandin (PG) D2, E2, F2 alpha, and 6-keto-PGF1 alpha was determined in homogenates of mouse, rat, and rabbit brain, and of rat cerebral blood vessels, using gas chromatography mass spectrometry. In all species tested, 6-keto-PGF1 alpha could be identified in the brain homogenates, but was a minor component in relation to other PGs. In contrast 6-keto-PGF1 alpha was the most abundant PG in the blood vessels, being present in about 40-fold higher levels than in the brain tissue. PGD2 was the most abundant PG in rat and mouse brains, but was below detection limits in the analyzed blood vessels. These studies indicating differential metabolism of PG endoperoxides in nervous and vascular tissue, provide a biochemical basis for further studies on the role of the PGs in brain circulation and neuronal activity.

Prostaglandin synthesis inhibition and monoamine metabolites in the rat brain.

The effect of indomethacin 3 mg/kg on levels of homovanillic acid (HVA), 4-hydroxy-3-methoxy phenyl ethylene glycol (HMPG) and 5-hydroxy indol acetic acid (5HIAA) was studied in rat striatum and olfactory tubercle with and without pretreatment with morphine 10 mg/kg. Indomethacin caused a small decrease in resting levels of HVA in striatum but not in olfactory tubercle. No effects were seen on resting or morphine induced changes in the levels of these monoamine metabolites. Likewise indomethacin 20 mg/kg failed to alter the elevation of HVA induced by chlorpromazine 15 mg/kg or the decrease of HVA induced by apomorphine (1--10 mg/kg) in the rat striatum. Our results do not support a major role for endogenous prostaglandins in the modulation of monoamine neurotransmission in the rat brain.

Determination of prostaglandin F2 alpha, E2, D2 and 6-keto-F1 alpha in human cerebrospinal fluid.

Prostaglandin (PG)F2 alpha, E2, D2 and 6-keto-F1 ALha were determined in human cerebrospinal fluid by a mass spectrometric technique. The samples were obtained from 12 patients with suspected intracranial disease. A 64 fold variation in PG levels was observed. The major PG was 6-keto-F1 alpha (0.12--15 ng/ml). PGF2 alpha and PGE2 were present in lower concentrations PGD2 was below the level of detection (0.05 ng/ml) except in one patient with extremely high total levels of PGs.

Regional and species differences in endogenous prostaglandin biosynthesis by brain homogenates.

Endogenously formed prostaglandins (PGs) D2, E2 and F2 alpha were determined in homogenates of brain regions from rat, guinea-pig, rabbit and cat, using gas-chromatography-mass spectrometry. The main PGs formed in the brain regions of the rat were PGD2, in the guinea-pig PGD2 and PGF2 alpha, in the rabbit PGF2 alpha and in the cat PGE2. Brain regions from the same animal species showed the same pattern of PG formation. They varied, however, in the amount of total PGs formed, the limbic system and the cerebral cortex being highest and cerebellum lowest.

Inhibition of prostaglandin synthesis in rat brain.

Rats were injected with one of five drugs alleged to inhibit brain prostaglandin (PG) synthesis: indomethacin, diclofenac, naproxen, aspiring and paracetamol. Animals were killed after 30 min. and the endogenous formation of PGF2alpha and PGE2 in brain homogenates was measured by mass fragmentography using deuterium labelled PGF2alpha and PGE2 as internal standards. Diclofenac, indomethacin, and naproxen inhibited dose dependently, the synthesis of PGF2alpha. The ED50 for diclofenac was 0.4 mg/kg, for indomethacin 1 mg/kg and for naproxen 2 mg/kg. In equieffective doses indomethacin had the longest duration. The time taken for the inhibition to decline to half its maximal value was 32 hrs for indomethacin and about 15 hrs for diclofenac and naproxen. Under the present conditions aspirin and paracetamol failed to produce significant reduction of PG synthesis in the rat brain homogenates in doses up to 100 mg/kg.

Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain.

Prostaglandin (PG) E2, D2, F2alpha and thromboxane B2 (TxB2) were determined in homogenates of rat brain by gas-chromatography--mass spectrometry. The level of PGD2 was 735 +/- 19 ng/g, of PGF2alpha 150 +/- 13 ng/g, of TxB2 112 ng/g and of PGE2 86 +/- 8 ng/g. The same relative proportions of cyclooxygenase products were found in incubates of unstimulated sliced rat brain. 14C-PGH2 was converted in high yield into PGD2 by enzyme(s) present in the soluble fraction of the homogenate. These results indicate that PGD2 is the major cyclooxygenase product in the central nervous system of the rat.