Histamine H(3) receptor-mediated inhibition of depolarization-induced, dopamine D(1) receptor-dependent release of [(3)H]-gamma-aminobutryic acid from rat striatal slices.
1. A study was made of the regulation of [(3)H]-gamma-aminobutyric acid ([(3)H]-GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H(3)-agonist. Depolarization-induced release of [(3)H]-GABA was Ca(2+)-dependent and was increased in the presence of the dopamine D(2) receptor family antagonist, sulpiride (10 microM). The sulpiride-potentiated release of [(3)H]-GABA was strongly inhibited by the dopamine D(1) receptor family antagonist, SCH 23390 (1 microM). Neither antagonist altered basal release. 2. The 15 mM K(+)-induced release of [(3)H]-GABA in the presence of sulpiride was inhibited by 100 microM histamine (mean inhibition 78+/-3%) and by the histamine H(3) receptor-selective agonist, immepip, 1 microM (mean inhibition 81+/-5%). The IC(50) values for histamine and immepip were 1.3+/-0.2 microM and 16+/-2 nM, respectively. The inhibitory effects of histamine and immepip were reversed by the H(3) receptor antagonist, thioperamide, 1 microM. 3. The inhibition of 15 mM K(+)-induced [(3)H]-GABA release by immepip was reversed by the H(3) receptor antagonist, clobenpropit, K(d) 0.11+/-0.04 nM. Clobenpropit alone had no effect on basal or stimulated release of [(3)H]-GABA. 4. Elevated K(+) caused little release of [(3)H]-GABA from striatal slices from reserpinized rats, unless the D(1) partial agonist, R(+)-SKF 38393, 1 microM, was also present. The stimulated release in the presence of SKF 38393 was reduced by 1 microM immepip to the level obtained in the absence of SKF 38393. 5. These observations demonstrate that histamine H(3) receptor activation strongly inhibits the dopamine D(1) receptor-dependent release of [(3)H]-GABA from rat striatum; primarily through an interaction at the terminals of GABA neurones.
Arias-Montaño
J A
JA
Department of Physiology, Biophysics and Neurosciences, Centro de Investigacion y de Estudios Avanzados, Apartado Postal 14-740, Mexico, D.F., Mexico.
Floran
B
B
Garcia
M
M
Aceves
J
J
Young
J M
JM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013469:Sulpiride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D065127:Dopamine D2 Receptor Antagonists; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018100:Receptors, Histamine H3; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D006632:Histamine; D012110:Reserpine; D013890:Thiourea; C052075:thioperamide; C086108:clobenpropit; D011188:Potassium; D002118:Calcium; D004298:Dopamine