Agonist-induced activation of histamine H3 receptor signals to extracellular signal-regulated kinases 1 and 2 through PKC-, PLD-, and EGFR-dependent mechanisms

Journal of Neurochemistry
Xiangru LaiNaiming Zhou

Abstract

The histamine H3 receptor (H3R), abundantly expressed in the central and the peripheral nervous system, has been recognized as a promising target for the treatment of various important CNS diseases including narcolepsy, Alzheimer's disease, and attention deficit hyperactivity disorder. The H3R acts via Gi/o -proteins to inhibit adenylate cyclase activity and modulate MAPK activity. However, the underlying molecular mechanisms for H3R mediation of the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) remain to be elucidated. In this study, using HEK293 cells stably expressing human H3R and mouse primary cortical neurons endogenously expressing mouse H3R, we found that the H3R-mediated activation of ERK1/2 was significantly blocked by both the pertussis toxin and the MEK1/2 inhibitor U0126. Upon stimulation by H3R agonist histamine or imetit, H3R was shown to rapidly induce ERK1/2 phosphorylation via PLC/PKC-, PLDs-, and epidermal growth factor receptor (EGFR) transactivation-dependent pathways. Furthermore, it was also indicated that while the βγ-subunits play a key role in H3R-activated ERK1/2 phosphorylation, β-arrestins were not required for ERK1/2 activation. In addition, when the cultured mouse cortical ...Continue Reading

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Citations

Oct 19, 2016·Molecular Pharmacology·Gustavo Nieto-AlamillaJosé-Antonio Arias-Montaño
Oct 3, 2017·Nature Nanotechnology·Eshan GhoshArun K Shukla
Apr 21, 2017·Molecular Pharmacology·Shuai XiaJianfeng Liu
Aug 7, 2017·Molecular and Cellular Biochemistry·Sajal ChakrabortiTapati Chakraborti
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Mar 1, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Xiaobai HeNaiming Zhou
Apr 20, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Qiang MaNaiming Zhou

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