Homologous down-regulation of histamine H3 receptors in rat striatal slices.
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Garduno-Torres B, Arias-Montano JA
Homologous down-regulation of histamine H3 receptors in rat striatal slices.
Synapse. 2006 Aug;60(2):165-71.
- PubMed ID
- 16715497 [ View in PubMed]
- Abstract
Preincubation of striatal slices with the selective histamine H3-receptor agonist immepip (100 nM) decreased the specific binding of N-alpha-[methyl-3H]-histamine ([3H]-NMHA) to membranes obtained from the treated slices. The binding decrease was significant after 5 min, remained at similar reduced levels between 5- and 30-min incubations with agonist, and only a partial recovery was observed after 90-min washout (34, 41, and 44% at 90, 120, and 150 min, respectively). Saturation analysis showed a significant decrease in both receptor density (-44% +/- 9%) and affinity (dissociation constant, Kd 1.15 +/- 0.23 nM from 0.59 +/- 0.17 nM). The effect of immepip was mimicked by histamine and the H3 agonists imetit and R-alpha-methylhistamine, and was blocked by the H3 antagonist thioperamide. The reduction in [3H]-NMHA binding was fully and partially prevented by incubation at 4 degrees C and in hypertonic medium, respectively, but not by the endocytosis inhibitor phenylarsine oxide (10 microM). None of the following protein kinase inhibitors, Ro-318220 and Go-6976 (PKC), H-89 (PKA) and staurosporine (general inhibitor) prevented the effect of immepip. In [3H]-adenine-labeled slices the preincubation with immepip (100 nM, 15 min) prevented the inhibitory effect of H3 receptor activation on forskolin-induced [3H]-cAMP accumulation (99% +/- 9% vs. 76% +/- 4% of control values). Taken together our results indicate that agonist binding promotes the down-regulation of striatal H3 receptors resulting in a significant loss of function.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Histamine Histamine H3 receptor Protein Humans YesAgonistDetails