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.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003988:Dibenzothiepins / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D008719:Methiothepin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D003988:Dibenzothiepins; D004146:Dioxanes; D012702:Serotonin Antagonists; D015016:Yohimbine; D008719:Methiothepin; D010134:Fenclonine; D011188:Potassium; D009638:Norepinephrine; D019329:Idazoxan