Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors.
In superfused mouse striatal slices preincubated with [3H]dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 mumol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [3H]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H3 agonist R-(-)-alpha-methylhistamine; it was not affected by the H1 antagonist dimetindene and the H2 antagonist ranitidine but abolished by the H3 antagonist thioperamide. Tritium overflow evoked by Ca2+ ions (introduced into Ca(2+)-free, K(+)-rich medium containing tetrodotoxin) was not affected by histamine 10 mumol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H3 receptor-mediated inhibition of dopamine release.
Schlicker
E
E
Institut für Pharmakologie und Toxikologie, Rheinische Freidrich-Wilhelms-Universität, Bonn, Federal Republic of Germany.
Fink
K
K
Detzner
M
M
Göthert
M
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010880:Piperidines / Q000494:pharmacology; D011968:Receptors, Histamine / Q000502:physiology*; D018100:Receptors, Histamine H3; D013237:Stereoisomerism; D013569:Synapses / Q000378:metabolism*; D014316:Tritium
D017442:Histamine Agonists; D008761:Methylhistamines; D010880:Piperidines; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D014316:Tritium; C069357:alpha-methylhistamine; D006632:Histamine; C052075:thioperamide; D002118:Calcium; D004298:Dopamine