Histamine H3 receptor activation inhibits glutamate release from rat striatal synaptosomes.
The release of glutamate from striatal synaptosomes induced by depolarisation with 4-aminopyridine (4-AP) was studied by a method based on the fluorescent properties of the NAPDH formed by the metabolism of the neurotransmitter by glutamate dehydrogenase.Ca(2+)-dependent, depolarisation-induced glutamate release was inhibited in a concentration-dependent manner by the selective histamine H(3) agonist immepip. Best-fit estimates were: maximum inhibition 60+/-10% and IC(50) 68+/-10 nM. The effect of 300 nM immepip on depolarisation-evoked glutamate release was reversed by the selective H(3) antagonist thioperamide in a concentration-dependent manner (EC(50) 23 nM, K(i) 4 nM). In fura-2-loaded synaptosomes, the increase in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) evoked by 4-AP-induced depolarisation (resting level 167+/-14 nM; Delta[Ca(2+)](i) 88+/-15 nM) was modestly, but significantly reduced (29+/-5% inhibition) by 300 nM immepip. The action of the H(3) agonist on depolarisation-induced changes in [Ca(2+)](i) was reversed by 100 nM thioperamide. Taken together, our results indicate that histamine modulates the release of glutamate from corticostriatal nerve terminals. Inhibition of depolarisation-induced Ca(2+) entry through voltage-dependent Ca(2+) channels appears to account for the effect of H(3) receptor activation on neurotransmitter release. Modulation of glutamatergic transmission in rat striatum may have important consequences for the function of basal ganglia and therefore for the control of motor behaviour.
Molina-Hernández
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Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Apdo. postal 14-740, 07000, D.F., Mexico, Mexico.
Nuñez
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Sierra
J J
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Arias-Montaño
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D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D010880:Piperidines; D018100:Receptors, Histamine H3; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D018698:Glutamic Acid; C052075:thioperamide