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

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 alpha 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.