Orexin-a activates phospholipase C- and protein kinase C-mediated Ca2+ signaling in dopamine neurons of the ventral tegmental area - PubMed (original) (raw)
Orexin-a activates phospholipase C- and protein kinase C-mediated Ca2+ signaling in dopamine neurons of the ventral tegmental area
K Uramura et al. Neuroreport. 2001.
Abstract
The orexin-orexin receptor system has been implicated in the regulation of wakefulness/sleep states. Behavioral and psycho-stimulant effects of orexins have also been shown. Mesolimbic dopamine neurons in the ventral tegmental area (VTA) are implicated in the regulation of reward and wakefulness/sleep, In the present study, we examined the effect of orexin-A on cytosolic [Ca2+]i concentration ([Ca2+]) in the isolated rat VTA dopamine neurons. Orexin-A (10-12-10-8 M) concentration dependently increased [Ca2+]i in dopamine-containing neurons. The [Ca2+]i responses to orexin-A were inhibited under Ca2+-free conditions and by blockers of voltage-gated L- and N-type [Ca2+]i channels, nitrendipine and omega-conotoxin, respectively. The [Ca2+]i responses were also abolished by a phosphatidylcholine-specific phospholipase C inhibitor, D609, and a protein kinase C (PKC) inhibitor, calphostin C. A PKC activator, TPA, mimicked orexin-A in increasing [Ca2+]i. These results indicate that orexin-A increases [Ca2+]i in VTA dopamine neurons via phosphatidylcholine-specific PLC- and PKC-mediated activation of L- and N-type Ca2+ channels. This effect may serve as the mechanism by which orexin regulates wakefulness/sleep states and exerts its behavioral and psychostimulant effects.
Similar articles
- Implication of protein kinase C in the orexin-induced elevation of extracellular dopamine levels and its rewarding effect.
Narita M, Nagumo Y, Miyatake M, Ikegami D, Kurahashi K, Suzuki T. Narita M, et al. Eur J Neurosci. 2007 Mar;25(5):1537-45. doi: 10.1111/j.1460-9568.2007.05403.x. Eur J Neurosci. 2007. PMID: 17425580 - Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine.
Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A. Borgland SL, et al. Neuron. 2006 Feb 16;49(4):589-601. doi: 10.1016/j.neuron.2006.01.016. Neuron. 2006. PMID: 16476667 - Excitatory effects of orexin-A on nucleus tractus solitarius neurons are mediated by phospholipase C and protein kinase C.
Yang B, Samson WK, Ferguson AV. Yang B, et al. J Neurosci. 2003 Jul 16;23(15):6215-22. doi: 10.1523/JNEUROSCI.23-15-06215.2003. J Neurosci. 2003. PMID: 12867505 Free PMC article. - Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction.
Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, Richardson KA. Aston-Jones G, et al. Brain Res. 2010 Feb 16;1314:74-90. doi: 10.1016/j.brainres.2009.09.106. Epub 2009 Oct 6. Brain Res. 2010. PMID: 19815001 Free PMC article. Review. - Roles of orexins in regulation of feeding and wakefulness.
Sakurai T. Sakurai T. Neuroreport. 2002 Jun 12;13(8):987-95. doi: 10.1097/00001756-200206120-00001. Neuroreport. 2002. PMID: 12060794 Review.
Cited by
- Distinct Neuromodulatory Effects of Endogenous Orexin and Dynorphin Corelease on Projection-Defined Ventral Tegmental Dopamine Neurons.
Mohammadkhani A, Qiao M, Borgland SL. Mohammadkhani A, et al. J Neurosci. 2024 Sep 25;44(39):e0682242024. doi: 10.1523/JNEUROSCI.0682-24.2024. J Neurosci. 2024. PMID: 39187377 Free PMC article. - Revolutionizing Infertility Management through Novel Peptide-based Targets.
Kumar V, Doshi G. Kumar V, et al. Curr Protein Pept Sci. 2024;25(9):738-752. doi: 10.2174/0113892037304433240430144106. Curr Protein Pept Sci. 2024. PMID: 38778605 Review. - Estradiol-dependent hypocretinergic/orexinergic behaviors throughout the estrous cycle.
Kim HJJ, Dickie SA, Laprairie RB. Kim HJJ, et al. Psychopharmacology (Berl). 2023 Jan;240(1):15-25. doi: 10.1007/s00213-022-06296-1. Epub 2022 Dec 26. Psychopharmacology (Berl). 2023. PMID: 36571628 Free PMC article. Review. - Orexin Signaling: A Complex, Multifaceted Process.
Dale NC, Hoyer D, Jacobson LH, Pfleger KDG, Johnstone EKM. Dale NC, et al. Front Cell Neurosci. 2022 Apr 13;16:812359. doi: 10.3389/fncel.2022.812359. eCollection 2022. Front Cell Neurosci. 2022. PMID: 35496914 Free PMC article. Review. - Role of Dopaminergic Receptors Within the Ventral Tegmental Area in Antinociception Induced by Chemical Stimulation of the Lateral Hypothalamus in an Animal Model of Orofacial Pain.
Matini T, Haghparast A, Rezaee L, Salehi S, Tehranchi A, Haghparast A. Matini T, et al. J Pain Res. 2020 Jun 15;13:1449-1460. doi: 10.2147/JPR.S255250. eCollection 2020. J Pain Res. 2020. PMID: 32606911 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous