Rainer K. Reinscheid
Associate Professor, Department of Pharmaceutical Sciences, College of Health Sciences
Joint Appointment, Pharmacology
Joint Appointment, Molecular Biology and Biochemistry
|molecular pharmacology, G protein-coupled receptors (GPCRs), neurophysiology, psychiatric disorders|
|URLs||Pharmaceutical Sciences Home Page|
|Pharmacology Home Page|
|Pharmacology Lab Page|
|Molecular Biology and Biochemistry|
|See below for selected publications or click here for additional publication listings available via PUB MED|
2003, Committee on Research Award, UCI, $11,800, “Molecular and functional characterization of prostaglandin receptors in colon cancer".
2004-06, Young Investigator's Award, National Alliance for Research on Schizophrenia and Depression (NARSAD), $60,000 direct costs, “A novel neuropeptide system in limbic thalamocortical structures and its role in schizophrenia”.
Our lab is interested in G protein-coupled receptors (GPCRs) and their physiological functions. We are studying GPCRs involved in stress, emotional behavior, sleep and wakefulness, and memory functions. The G protein-coupled receptors (GPCRs) are the biggest gene family in the human genome and represent the most successful drug targets of modern pharmaceuticals. With the sequence of the human genome at hand we now know, that there are at least 150 so-called "orphan" GPCRs which still await discovery of their natural ligands.
As one example, we have been working on the neuropeptide Orphanin FQ (OFQ; also called nociceptin) which we identified in 1995 as the endogenous ligand of an opioid-like receptor. We could demonstrate that OFQ is involved in stress regulation and anxiety behavior. A knockout mouse lacking the OFQ precursor protein shows increased susceptibility to stress and impaired adaptation to repeated stress, but is resistant to the development of morphine tolerance. A malfunction of the OFQ system might thus be involved in the pathology of human psychiatric diseases such as depression, anxiety or drug addiction.
More recently, we have identified a novel neuropeptide system (Neuropeptide S) in the brain that promotes arousal and anxiolytic-like effects. We are currently investigating the function of NPS in sleep and wakefulness, and its role in stress responses and learning & memory.
Our group uses molecular biology, cell biology, anatomical analysis, physiological and behavioral assays, and transgenic techniques to address fundamental questions about in-vivo functions of novel receptor-ligand systems, ranging from single cells to whole animal behavior.
Reinscheid, R.K., Nothacker, H.-P., Bourson, A., Ardati, A., Henningsen, R.A., Bunzow, J.R., Grandy, D.K., Langen, H., Monsma, F.J. & Civelli, O. (1995) Orphanin FQ: A novel neuropeptide that activates an opioidlike G protein-coupled receptor. Science 270: 792-794.
Reinscheid, R.K., Ardati, A., Monsma, F.J. & Civelli, O. (1996) Structure-activity relationship studies on the novel neuropeptide orphanin FQ. J. Biol. Chem. 271: 14163-14168.
Nothacker, H.-P., Reinscheid, R.K., Mansour, A., Henningsen, R.A., Ardati, A., Monsma, F.J., Watson, S.J. & Civelli, O. (1996) Primary structure and tissue distribution of the orphanin FQ precursor. Proc. Natl. Acad. Sci. U.S.A. 93: 8677-8682.
Knoflach, F., Reinscheid, R.K., Civelli, O. & Kemp, J.A. (1996) Modulation of voltage-gated calcium channels by orphanin FQ in freshly dissociated hippocampal neurons. J. Neurosci. 16: 6657-6664.
Meng, F., Taylor, L.P., Hoversten, M.T., Ueda, Y., Ardati, A., Reinscheid, R. K., Monsma, F.J., Watson, S.J., Civelli, O. & Akil, H. (1996) Moving from the orphanin FQ receptor to an opioid receptor using four point mutations. J. Biol. Chem. 271: 32016-32020.
Jenck, F., Moreau, J.-L., Martin, J.R., Kilpatrick, G.J., Reinscheid, R.K., Monsma, F.J., Nothacker, H.-P. & Civelli, O. (1997) Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress. Proc. Natl. Acad. Sci. U.S.A. 94: 14854-14858.
Reinscheid, R.K., Higelin, J., Henningsen, R.A., Monsma, F.J. & Civelli, O. (1998) Structures that delineate orphanin FQ and dynorphin A pharmacological selectivities. J. Biol. Chem. 273: 1490-1495.
Köster, A., Montkowski, A., Schulz, S., Stübe, E.-M., Knaudt, K., Jenck, F., Moreau, J.-L., Nothacker, H.-P., Civelli, O. & Reinscheid, R.K. (1999) Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice. Proc. Natl. Acad. Sci. U.S.A. 96: 10444-10449.
Nothacker, H.-P., Wang, Z., Zhu, Y., Reinscheid, R.K., Lin, S. & Civelli, O. (2000) Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: Discovery of a subtype-selective ligand. Mol. Pharmacol. 58: 1601-1608.
Civelli, O., Nothacker, H.-P., Saito, Y., Wang, Z., Lin, S.H. & Reinscheid, R.K. (2001) Novel neurotransmitters as natural ligands of orphan G-protein-coupled receptors. Trends Neurosci. 24: 230-237.
Bregola, G., Zucchini, S., Rodi, D., Binaschi, A., D'Addario, C., Landuzzi, D., Reinscheid R.K., Candeletti, S., Romualdi, P. & Simonato, M. (2002) Involvement of the neuropeptide Nociceptin/Orphanin FQ in kainate-induced seizures. J. Neurosci. 22: 10030-10038.
Depner, U.B., Reinscheid, R.K., Takeshima, H., Brune, K. & Zeilhofer, H.U. (2003) Normal sensitivity to acute pain, but increased inflammatory hyperalgesia in mice lacking the nociceptin precursor polypeptide or the nociceptin receptor. Eur. J. Neurosci. 17: 2381-2387.
Xu, Y.-L., Reinscheid, R.K., Huitron-Resendiz, S., Clark, S.D., Wang, Z., Lin, S.H., Brucher, F.A., Zeng, J., Ly, N.K., Henriksen, S.J., de Lecea, L. & Civelli, O. (2004) Neuropeptide S: A neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43: 487–497.
Reinscheid, R.K., Xu, Y.L., Okamura, N., Zeng, J., Chung, S., Pai, R., Wang, Z. & Civelli, O. (2005) Pharmacological characterization of human and murine Neuropeptide S receptor variants. J. Pharmacol. Exp. Therap. 315: 1338-1345.
Okuda-Ashitaka, E., Minami, T., Matsumura, S., Takeshima, H., Reinscheid, R.K., Civelli, O. & Ito, S. (2006) The opioid peptide nociceptin/orphanin FQ mediates prostaglandin E2-induced allodynia, tactile pain associated with nerve injury. Eur. J. Neurosci. 23: 995-1004.
Chung, S., Pohl, S., Zeng, J., Civelli, O. & Reinscheid, R.K. (2006) Endogenous orphanin FQ / nociceptin is involved in the development of morphine tolerance. J. Pharmacol. Exp. Therap. 318: 262-267.
Xu, Y.L., Gall, C.M., Jackson, V.R., Civelli, O. & Reinscheid, R.K. (2006) Distribution of Neuropeptide S receptor mRNA and neurochemical characteristics of Neuropeptide S expressing neurons in the rat brain. J. Comp. Neurol., 500: 84-102.
Okamura, N., Hashimoto, K., Iyo, M., Shimizu, E., Dempfle, A., Friedel, S. & Reinscheid, R.K. (2007) Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder. Prog. Neuropharmacol. Biol. Psychiatry 31: 1444-1448
Okamura, N., Habay, S.A., Zeng, J., Chamberlin, A.R. & Reinscheid, R.K. (2008) Synthesis and pharmacological in vitro and in vivo profile of SHA 68 (3-Oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide), a selective antagonist of the Neuropeptide S receptor. J. Pharmacol. Exp. Ther. 325: 893-901
Mohanty, S. K., Reinscheid, R. K., Liu, X., Okamura, N., Krasieva, T. & Berns, M. W. (2008) In-depth activation of channelrhodopsin 2 sensitized excitable cells with high spatial resolution using two-photon excitation with near-IR laser microbeam. Biophys. J. 95: 3916-3926
Jüngling, K., Seidenbecher, T., Sosulina, L., Lesting, J., Sangha, S., Clark, S.D., Okamura, N., Duangdao, D.M., Xu, Y.L., Reinscheid, R.K. & Pape, H.C. (2008) Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala. Neuron 59: 298-310
Okamura, N., Reinscheid, R.K., Ohgake, S., Iyo, M. & Hashimoto, K. (2010) Neuropeptide S attenuates neuropathological, neurochemical and behavioral changes induced by the NMDA receptor antagonist MK-801. Neuropharmacology 58: 166-172
Si, W., Aluisio, L., Okamura, N., Clark, S.D., Fraser, I., Sutton, S.W., Bonaventure, P. & Reinscheid, R.K. (2010) Neuropeptide S stimulates dopaminergic neurotransmission in the medial prefrontal cortex. J. Neurochem. 115: 475-482
Okamura, N., Garau, C., Duangdao, D.M., Clark, S.D., Jüngling, K., Pape, H.C. & Reinscheid, R.K. (2010) Neuropeptide S enhances memory consolidation and interacts with noradrenergic systems in the brain. Neuropsychopharmacology, 2010 Dec 8, epub ahead of print
Society for Neuroscience
International Narcotics Research Conference (INRC)
International Neuroendocrine Federation (INF)
Sleep Research Society
Cellular and Molecular Biosciences
Interdepartmental Neuroscience Program
Medicinal Chemistry and Pharmacology
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|(This faculty member is (or was) affiliated with UCI, but does not currently have an active appointment with UCI.)|