Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum.
Unilateral 6-hydroxydopamine lesion to rat substantia nigra pars compacta resulted in a modest, but significant, decrease in the specific binding of N-alpha-[methyl-3H]histamine (19 +/- 5% reduction) to synaptosomal membranes from ipsilateral striata. Dopamine synthesis was assessed in striatal slices by determining [3H]DOPA accumulation after inhibition of DOPA decarboxylase. [3H]DOPA synthesis induced by 50 mM K+ (151 +/- 4% of basal) was prevented by either Ca2+ removal or by Ni2+. Depolarization-stimulated [3H]DOPA accumulation was reduced by the selective H3-agonist immepip (100 nM; 68 +/- 7% inhibition). The effect of immepip was reversed by thioperamide (100 nM), a selective H3-antagonist. Taken together, our results indicate that histamine modulates striatal dopamine synthesis by acting at H3-receptors located on dopaminergic nerve terminals.
Molina-Hernández
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Departamento de Fisiología, Biofisica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México DF, México.
Nuñez
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Arias-Montaño
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JA
D000818:Animals; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D017442:Histamine Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D011188:Potassium / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D013565:Sympatholytics / Q000633:toxicity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D017442:Histamine Agonists; D008761:Methylhistamines; D018377:Neurotransmitter Agents; D018100:Receptors, Histamine H3; D013565:Sympatholytics; D004295:Dihydroxyphenylalanine; C069357:alpha-methylhistamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D004298:Dopamine