Pharmacological antagonism of histamine H2R ameliorated L-DOPA-induced dyskinesia via normalization of GRK3 and by suppressing FosB and ERK in PD.

Pharmacological antagonism of histamine H2R ameliorated L-DOPA-induced dyskinesia via normalization of GRK3 and by suppressing FosB and ERK in PD. Neurobiol Aging. 2019 Jun 19;81:177-189 Authors: Ahmed MR, Jayakumar M, Ahmed MS, Zamaleeva AI, Tao J, Li EH, Job JK, Pittenger C, Ohtsu H, Rajadas J Abstract Parkinson's disease (PD) is often managed with L-3,4-dihydroxyphenylalanine (L-DOPA), which is still the gold standard to relieve the clinical motor symptoms of PD. However, chronic use of L-DOPA leads to significant motor complications, especially L-DOPA-induced dyskinesia (LID), which limit the therapeutic benefit. Few options are available for the pharmacological management of LID partly due to the inadequacy of our mechanistic understanding of the syndrome. We focused on the role of the histamine (HA) H2 receptor (H2R) in the striatum, which others have shown to be involved in the development of LID. We generated LID in a hemiparkinsonian mouse model and tested the signaling effects of ranitidine, an H2R antagonist. We used histidine decarboxylase deficient mice (Hdc-Ko) which lacks HA to study the role of G-protein-coupled receptor kinases (GRKs) in HA deficiency. Loss of HA in Hdc-Ko mice did not result in the downregulation of GRKs, especially GRK3 and GRK6, which were previously found to be reduced in hemiparkinsonian animal models. Ranitidine, when given along with L-DOPA, normalized the expression of GRK3 in the dopamine-de...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research