Influence of eicosanoids on serotonin release in the rat brain: inhibition by prostaglandins E1 and E2.

Abstract

Superfused rat brain cortex slices, hypothalamic slices and cortex synaptosomes preincubated with 3H-serotonin or 3H-noradrenaline were used to study the effects of eicosanoids on tritium overflow evoked either electrically (3 Hz; slices) or by potassium 12 mmol/l (synaptosomes). 1. The electrically evoked 3H overflow from cortex slices preincubated with 3H-serotonin was inhibited by prostaglandins E1 and E2 and by the prostacyclin analogue iloprost. No effect was seen with prostaglandin F2 alpha, prostaglandin D2, CG 4203 (another prostacyclin analogue), U 46619 (a thromboxane A2 analogue) and leukotriene C4. The same held true for indomethacin and the prostaglandin receptor antagonists SC 19220 and N-0164. The inhibitory effect of prostaglandin E2 was slightly more pronounced in the presence of indomethacin than in its absence, but was not affected by SC 19220, N-0164 or forskolin plus AH 21-132 (an inhibitor of cAMP phosphodiesterase). Yohimbine and the serotonin receptor antagonist metitepin failed to influence the inhibitory effect of prostaglandin E1. 2. The potassium-evoked 3H overflow from cortex synaptosomes preincubated with 3H-serotonin was inhibited by prostaglandin E2. 3. Prostaglandin E2 also inhibited the electrically evoked 3H overflow from hypothalamic slices preincubated with 3H-serotonin. 4. The electrically evoked 3H overflow from cortex slices preincubated with 3H-noradrenaline was inhibited by prostaglandin E2, but was not affected by SC 19220, which, in turn, did also not alter the effect of prostaglandin E2. The present results are compatible with the view that presynaptic SC 19220-insensitive prostaglandin E receptors may be involved in the inhibitory effect of prostaglandins E1 and E2 on serotonin (and noradrenaline) release.