Effects of L-threo-3,4-dihydroxyphenylserine on efflux of monoamines and acetylcholine in guinea pig brain.
The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the release of monoamines and acetylcholine (ACh) was studied in the superfused brain slices of guinea pig. In the tissues preloaded either with [3H]norepinephrine ([3H]NE), [3H]dopamine ([3H]DA), [3H]-5-hydroxytryptamine or [3H]choline, tritium effluxes were estimated in serial fractions of superfusates. L-threo-DOPS produced a concentration-dependent increase in the spontaneous efflux of [3H]NE both in the cortical and hypothalamic slices and to a lesser extent that of [3H]DA in the striatal slices. These effects were still fully detected when slices were superfused with a calcium-free medium or tetrodotoxin (10(-6) M). Carbidopa at 5 X 10(-4) M but not at 10(-4) M significantly depressed the [3H]catecholamine effluxes induced by L-threo-DOPS. L-threo-DOPS produced a minimum increase in the spontaneous efflux of [3H]-5-hydroxytryptamine but not that of [3H]ACh. L-threo-DOPS (5 X 10(-4) M) significantly reduced the [3H]ACh efflux from electrically stimulated striatal slices and this effect was antagonized by an alpha-2 adrenoceptor antagonist yohimbine (10(-6) M) or by a D2 DA receptor antagonist sulpiride (10(-6) M). In vivo, L-threo-DOPS (150 mg/kg i.p.) produced a gradual but long-lasting increase in the efflux of [3H]NE from the parietal cortex of the guinea pig pretreated with carbidopa (20 mg/kg i.p.). In the brain homogenates, L-threo-DOPS (10(-10) to 10(-4) M) itself did not inhibit the bindings of [3H]rauwolscine or [3H]spiperone, specific ligands for labeling alpha-2 and D2 receptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015103:Droxidopa / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D012694:Serine / Q000031:analogs & derivatives*; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D012694:Serine; D015103:Droxidopa; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine