INHIBITION OF MONOAMINE OXIDASE-B BY (-)-DEPRENYL POTENTIATES NEURONAL RESPONSES TO DOPAMINE AGONISTS BUT DOES NOT INHIBIT DOPAMINE CATABOLISM IN THE RAT STRIATUM
被引:1
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作者:
PATERSON, IA
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PATERSON, IA
JUORIO, AV
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JUORIO, AV
BERRY, MD
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BERRY, MD
ZHU, MY
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ZHU, MY
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来源:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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1991年
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258卷
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03期
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中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
This report describes experiments designed to determine whether (-)-deprenyl potentiates dopaminergic transmission and whether its mechanism involves the inhibition of dopamine catabolism. Intraperitoneal administration of (-)-deprenyl (0.5-8 mg kg-1) produced a dose-dependent inhibition of striatal monoamine oxidase type B activity whereas monoamine oxidase type A activity in the striatum was inhibited only by 8 mg kg-1 of (-)-deprenyl. Intraperitoneal administration of (-)-deprenyl (0.5-4 mg kg-1) did not alter the striatal concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or homovanillic acid. DOPAC concentrations were decreased by 8 mg kg-1 of (-)-deprenyl. In contrast, administration of clorgyline (2 mg kg-1), a monoamine oxidase type A inhibitor, increased the striatal concentrations of DA and decreased the striatal concentrations of DOPAC and homovanillic acid. The striatal concentrations of 2-phenylethylamine (PE), a putative modulator of striatal DA transmission, were increased by (-)-deprenyl (1-8 mg kg-1) but were unaffected by clorgyline (2 mg kg-1). In electrophysiological studies, single caudate neuron responses to iontophoretically applied (-)-apomorphine and (+/-)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin were potentiated by intracarotid injections of PE (30-mu-g kg-1) and i.p. injections of (-)-deprenyl (2 mg kg-1). Both PE and (-)-deprenyl reduced the IT50 of responses to apomorphine and (+/-)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin. It is concluded that acute administration of (-)-deprenyl can potentiate striatal dopaminergic transmission by a mechanism which does not depend on the inhibition of DA catabolism. It is proposed that (-)-deprenyl acts indirectly by increasing the striatal concentration of PE, which in turn potentiates dopaminergic transmission.
机构:
Kings Coll London, Pharmacol Grp, Div Biomed Sci, Neurodegenerat Dis Res Ctr, London SW3 6LX, EnglandKings Coll London, Pharmacol Grp, Div Biomed Sci, Neurodegenerat Dis Res Ctr, London SW3 6LX, England
Rose, S
Hindmarsh, JG
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机构:
Kings Coll London, Pharmacol Grp, Div Biomed Sci, Neurodegenerat Dis Res Ctr, London SW3 6LX, EnglandKings Coll London, Pharmacol Grp, Div Biomed Sci, Neurodegenerat Dis Res Ctr, London SW3 6LX, England
Hindmarsh, JG
Jenner, P
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机构:
Kings Coll London, Pharmacol Grp, Div Biomed Sci, Neurodegenerat Dis Res Ctr, London SW3 6LX, EnglandKings Coll London, Pharmacol Grp, Div Biomed Sci, Neurodegenerat Dis Res Ctr, London SW3 6LX, England