Prof Sue Wonnacott
Profile
Research interests
Research in the Wonnacott lab is focussed on nicotinic acetylcholine receptors (nAChRs). These are pentameric ligand-gated cation channels that are activated by the neurotransmitter acetylcholine. They take their name from the agonist action of nicotine on these molecules. nAChRs at the nerve-muscle synapse have been very well characterized, but a family of unique subunits is expressed in the nervous system, with the potential for forming a large variety of nAChR subtypes. These exert a subtle influence on neuronal activity, by modulating transmitter release and cell signalling events, including intracellular calcium levels and gene transcription.
Some brain nAChRs are the site of action of doses of nicotine encountered during tobacco smoking, and mediate the psychoactive and addictive properties of the drug. nAChRs are also regarded as potential therapeutic targets for a number of brain disorders, including Alzheimer’s and Parkinson’s diseases, schizophrenia and attention deficit hyperactivity disorder. Understanding the molecular and cellular events underlying the effects of acute and chronic nAChR stimulation is a major goal of our research. Research in this laboratory is funded by grants and studentships from the Research Councils, The Wellcome Trust and links with the pharmaceutical industry.
Goals: To elucidate the structure, function and regulation of neuronal nicotinic receptors in health and disease.
Current projects:
- Comparison of nAChR subtypes regulating noradrenaline release in rat hippocampus and frontal cortex, in vitro and in vivo (in collaboration with RenaSci, Nottingham);
- Characterization of alpha7 nAChRs and their downstream signalling targets in brain and primary cultures (in collaboration with Pfizer);
- Role of alpha7 nAChRs in APP processing (in collaboration with Dr Rob Williams, Bath)
Publications
Bennett, H. M., Lees, K., Harper, K. M., Jones, A. K., Sattelle, D. B., Wonnacott, S. and Wolstenholme, A. J., 2012. Xenopus laevis RIC-3 enhances the functional expression of the C. elegans homomeric nicotinic receptor, ACR-16, in Xenopus oocytes. Journal of Neurochemistry, 123 (6), pp. 911-918.
Kennett, A., Heal, D. J. and Wonnacott, S., 2012. Pharmacological differences between rat frontal cortex and hippocampus in the nicotinic modulation of noradrenaline release implicate distinct receptor subtypes. Nicotine & Tobacco Research, 14 (11), nts128.
Quik, M. and Wonnacott, S., 2011. α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease. Pharmacological Reviews, 63 (4), pp. 938-966.
del Barrio, L., Martin-de-Saavedra, M. D., Romero, A., Parada, E., Egea, J., Avila, J., McIntosh, J. M., Wonnacott, S. and Lopez, M. G., 2011. Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by alpha 7 and beta 2*Nicotinic Stimulation. Toxicological Sciences, 123 (1), pp. 193-205.
Glendinning, S. K., Buckingham, S. D., Sattelle, D. B., Wonnacott, S. and Wolstenholme, A. J., 2011. Glutamate-Gated Chloride Channels of Haemonchus contortus Restore Drug Sensitivity to Ivermectin Resistant Caenorhabditis elegans. PLoS ONE, 6 (7), e22390.
Iturriaga-Vasquez, P., Carbone, A., Garcia-Beltran, O., Livingstone, P. D., Biggin, P. C., Cassels, B. K., Wonnacott, S., Zapata-Torres, G. and Bermudez, I., 2010. Molecular determinants for competitive inhibition of alpha 4 beta 2 nicotinic acetylcholine receptors. Molecular Pharmacology, 78 (3), pp. 366-375.
Innocent, N., Evans, N., Hille, C. and Wonnacott, S., 2010. Oligomerisation differentially affects the acute and chronic actions of amyloid-β in vitro. Neuropharmacology, 59 (4-5), pp. 343-352.
Kennett, A. F., Heal, D. and Wonnacott, S., 2010. Investigating the subtypes of nocotinic achr involved in catecholamine release in different regions of the rodent brain. Journal of Psychopharmacology, 24 (Supplement 3), A32.
Wonnacott, S. and Livingstone, P. D., 2010. Nicotinic receptors and the modulation of transmitter release in the prefrontal cortex. European Neuropsychopharmacology, 20 (Supplement 3), S193.
Araud, T., Wonnacott, S. and Bertrand, D., 2010. Associated proteins: the universal toolbox controlling ligand gated ion channel function. Biochemical Pharmacology, 80 (2), pp. 160-169.
Abin-Carriquiry, J. A., Zunini, M. P., Cassels, B. K., Wonnacott, S. and Dajas, F., 2010. In silico characterization of cytisinoids docked into an acetylcholine binding protein. Bioorganic & Medicinal Chemistry Letters, 20 (12), pp. 3683-3687.
Livingstone, P. D., Dickinson, J. A., Srinivasan, J., Kew, J. N. C. and Wonnacott, S., 2010. Glutamate-Dopamine Crosstalk in the Rat Prefrontal Cortex is Modulated by Alpha7 Nicotinic Receptors and Potentiated by PNU-120596. Journal of Molecular Neuroscience, 40 (1-2), pp. 172-176.
Abin-Carriquiry, J. A., Urbanavicius, J., Scorza, C., Rebolledo-Fuentes, M., Wonnacott, S., Cassels, B. K. and Dajas, F., 2010. Increase in locomotor activity after acute administration of the nicotinic receptor agonist 3-bromocytisine in rats. European Journal of Pharmacology, 634 (1-3), pp. 89-94.
Rushforth, S. L., Allison, C., Wonnacott, S. and Shoaib, M., 2010. Subtype-selective nicotinic agonists enhance olfactory working memory in normal rats: A novel use of the odour span task. Neuroscience Letters, 471 (2), pp. 114-118.
Kennett, A., Heal, D. and Wonnacott, S., 2009. Distinct pharmacological profiles for nicotinic AChR-evoked noradrenaline release in rat frontal cortex and hippocampus. Biochemical Pharmacology, 78 (7), pp. 915-916.
Livingstone, P. D., Hockley, J. and Wonnacott, S., 2009. Nicotinic acetylcholine receptors differentially regulate phosphorylation of dopamine target cell proteins in the rat prefrontal cortex. Biochemical Pharmacology, 78 (7), p. 909.
Livingstone, P. D. and Wonnacott, S., 2009. Nicotinic acetylcholine receptors and the ascending dopamine pathways. Biochemical Pharmacology, 78 (7), pp. 744-755.
Quarta, D., Naylor, C. G., Barik, J., Fernandes, C., Wonnacott, S. and Stolerman, I. P., 2009. Drug discrimination and neurochemical studies in alpha 7 null mutant mice: tests for the role of nicotinic alpha 7 receptors in dopamine release. Psychopharmacology, 203 (2), pp. 399-410.
Livingstone, P. D., Srinivasan, J., Kew, J. N. C., Dawson, L. A., Gotti, C., Moretti, M., Shoaib, M. and Wonnacott, S., 2009. α7 and non-α7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex. European Journal of Neuroscience, 29 (3), pp. 539-550.
Barik, J. and Wonnacott, S., 2009. Molecular and cellular mechanisms of action of nicotine in the CNS. In: Henningfield, J. E., London, E. D. and Pogun, S., eds. Nicotine Psychopharmacology. Vol. 192. Berlin: Springer, pp. 173-207.
Innocent, N., Livingstone, P. D., Hone, A., Kimura, A., Young, T., Whiteaker, P., McIntosh, J. M. and Wonnacott, S., 2008. Aplha-Conotoxin Arenatus IB[V11L,V16D] Is a Potent and Selective Antagonist at Rat and Human Native 7 Nicotinic Acetylcholine Receptors. Journal of Pharmacology and Experimental Therapeutics, 327 (2), pp. 529-537.
Dickinson, J. A., Kew, J. N. C. and Wonnacott, S., 2008. Presynaptic α7- and β2-containing nicotinic acetylcholine receptors modulate excitatory amino acid release from rat prefrontal cortex nerve terminals via distinct cellular mechanisms. Molecular Pharmacology, 74 (2), pp. 348-359.
Abin-Carriquiry, J., Costa, G., Urbanavicius, J., Cassels, B., Rebolledo-Fuentes, M., Wonnacott, S. and Dajas, F., 2008. In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: Implications for Parkinson's Disease. European Journal of Pharmacology, 589 (1-3), pp. 80-84.
Wonnacott, S., 2008. Smoking cessation 2008. IDrugs, 11 (4), pp. 256-259.
Hanrott, K., Murray, T. K., Orfali, Z., Ward, M., Finlay, C., O'Neill, M. J. and Wonnacott, S., 2008. Differential activation of PKCδ in the substantia nigra of rats following striatal or nigral 6-hydroxydopamine lesions. European Journal of Neuroscience, 27 (5), pp. 1086-1096.
Wonnacott, S., 2008. Gates and filters: unveiling the physiological roles of nicotinic acetylcholine receptors in dopaminergic transmission. British Journal of Pharmacology, 153 (S1), S2-S4.
