Methiothepin enhances the potassium-evoked release of [3H]-noradrenaline in rat pineal gland

Summary The 5-hydroxytryptamine (5-HT) autoreceptor antagonist methiothepin increased in a concentration-dependent manner the K⁺-evoked release of [³H]-noradrenaline in pineal glands from normal and parachlorophenylalanine (PCPA)-treated rats. However, 5-HT and the 5-HT receptor agonists, LSD and 5-methoxytryptamine, were inactive at modulating the K⁺-evoked release of [³H]-noradrenaline in pineal glands from normal and PCPA-treated rats. When tested on the uptake of [³H]-noradrenaline in the pineal gland, methiothepin was found to be a potent inhibitor (IC₅₀ = 10.6 nmol/l). Exposure to methiothepin failed to increase the K⁺-evoked release of [³H]-noradrenaline when tested in the presence of cocaine. While the K⁺-evoked release of [³H]-noradrenaline was shown to be modulated through inhibitory presynaptic ₂-adrenoceptors in pineal glands from normal and PCPA-treated rats, no evidence was obtained for a presynaptic modulation through 5-HT receptors of [³H]-noradrenaline release. The facilitation by methiothepin of the K⁺-evoked release of [³H]-noradrenaline in rat pineal gland appears to be due to the inhibition of noradrenaline uptake by this compound.Some of the results were presented at the Meeting of the British Pharmacological Society (Galzin et al. 1986)Send offprint requests to S. Z. Langer