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Professor Amanda Page
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A/Prof Amanda page has established herself as a leading authority on vagal innervation of the gut, and how this relates to major disease states including obesity and gastro-oesophageal reflux disease. This has involved pioneering studies on the phenotypic specialisation of vagal sensory endings and a classification of gastrointestinal sensory nerves that has been adopted world-wide. One of her major findings, that GABAB receptor agonists inhibit peripheral gastro-oesophageal vagal afferent endings, prompted 2 full scale drug development programs and the production of 5 patents. Investigation of the effects of different nutritional states (e.g food restriction and excess) on these afferents has resulted in major contributions in the understanding of gastric satiety signalling.
NHMRC grant no. 565186
Chief Investigators: Dr. AJ Page (CIA), Pr G Wittert Pr D Kennaway
Title: Circadian control of peripheral gastric satiety signals.
NHMRC grant no. 1023972
Chief Investigators: Dr. AJ Page (CIA), A/Pr LA Blackshaw, Pr G Wittert and Dr SM Brierley
Title: Role of adipokines in gastric satiety signalling.
NHMRC grant no. 565186
Chief Investigators: Dr. AJ Page (CIA), A/Pr LA Blackshaw and Pr G Wittert
Title: Interactions of gastric hormones with vagal afferent pathways and the role of this system in obesity.
NHMRC grant no. 399324
Chief Investigators: A/Pr LA Blackshaw, A/Pr S Brookes, Dr S. Brierley and Dr. AJ Page (CID)
Title: How does inflammation of the gut change its sensory innervation?
NHMRC grant no. 298942
Chief Investigators: A/Pr LA Blackshaw, Dr. AJ Page (CIB) & Dr S. Brierley
Title: Mechanisms of mechanotransduction in primary visceral afferents.
NHMRC grant no. 104814
Chief Investigators: A/Pr LA Blackshaw & Dr. AJ Page (CIB)
Title: Gastrointestinal sensory function in normal and diseased states.
1. Vials AJ & Burnstock G. Effects of nitric oxide synthase inhibitors , L-NG-nitroarginine and L-NG-nitroarginine methyl esther, on responses to vasodilators of the guinea-pig coronary vasculature. British Journal of Pharmacology 1992; 107: 604-609.
2. Vials AJ & Burnstock G. A2-purinoceptor-mediated relaxation in the guinea-pig coronary vasculature: A role for nitric oxide. British Journal of Pharmacology 1993; 109: 424-429.
3. Vials AJ & Burnstock G. Effects of pyrimidines on the guinea-pig coronary vasculature. British Journal of Pharmacology 1993; 110: 1091-1097.
4. Vials AJ & Burnstock G. The effects of suramin on relaxant vasodilator responses to ATP and 2-methylthioATP in the sprague-Dawley rat coronary vasculature. European Journal of Pharmacology. 1994; 251: 299-302.
5. Vials AJ & Burnstock G. Differential effects of ATP- and 2-methylthioATP-induced relaxation in guinea-pig coronary vasculature. Journal of Cardiovascular Pharmacology. 1994; 23: 757-764.
6. Vials AJ & Burnstock G.ATP release from the isolated perfused guinea-pig heart in response to increased flow. Journal of Vascular Research. 1996; 33: 1-4.
7. Stones RW, Vials AJ, Milner P, Beard RW & Burnstock G. Release of vasoactive agents from the isolated perfused human ovary. European Journal of Obstetrics and Gynaecology and Reproductive Biology. 1996; 67: 191-196.
8. Vials AJ, Crowe R & Burnstock G. A neuromodulatory role for neuronal nitric oxide in the rabbit renal artery. British Journal of Pharmacology. 1997; 121: 213-220.
9. Page AJ & Blackshaw LA. An in vitro study of the properties of vagal afferent fibres innervating the ferret oesophagus and stomach. Journal of Physiology. 1998; 512: 907-916.
10. Smid SD, Page AJ, O’Donnell T, Langman J, Rowland R & Blackshaw LA. Oesophagitis-induced changes in capsaicin-sensitive tachykininergic pathways in the ferret lower oesophageal sphincter. Neurogastroenterology & Motility. 1998; 10: 403-411.
11. Page AJ & Blackshaw LA. GABAB receptors inhibit mechanosensitivity of primary afferent endings. Journal of Neuroscience. 1999; 19: 8597-8602.
12. Blackshaw LA, Page AJ & Partosoedarso ER. Acute effects of capsaicin on gastrointestinal vagal afferents. Neuroscience. 2000; 279; 157-162.
13. Blackshaw LA, Page AJ, Smid S, Dent J, and Lehmann A. GABAB receptors – peripheral and central targets for controlling gastro-oesophageal reflux. Current Opinion in Central and Peripheral Nervous System Investigational Drugs 2000; 2: 333-343.
14. Page AJ, O’Donnell T & Blackshaw LA. P2X receptor-induced sensitization of vagal mechanoreceptors in oesophageal inflammation. Journal of Physiology. 2000; 523: 403-411.
15. Page AJ, Martin CM & Blackshaw LA. Vagal mechanoreceptors and chemoreceptors in mouse stomach and esophagus. Journal of Neurophysiology, 2002; 87: 2095-2103.
16. Page AJ, Brierley SM, Martin CM, Martinez-Salgado C, Wemmie JA, Brennan TJ, Symonds E, Omari T, Lewin GR, Welsh MJ, Blackshaw LA. The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function. Gastroenterology 2004; 127:1739-47.
17. Page AJ, Young RL, Martin CM, Umaerus M, O'Donnell TA, Cooper NJ, Coldwell JR, Hulander M, Mattsson JP, Lehmann A and Blackshaw LA. Metabotropic glutamate receptors inhibit mechanosensitivity in vagal sensory neurons. Gastroenterology 2005; 128:402-410.
18. Page AJ, Slattery JA, O'Donnell TA, Cooper NJ, Young RL and Blackshaw LA. Modulation of gastro-oesophageal vagal afferents by galanin in mouse and ferret. Journal of Physiology 2005; 563:809-819.
19. Page AJ, Brierley SM, Martin CM, Price MP, Symonds E, Butler R, Wemmie JA, Blackshaw LA. Different contributions of ASIC channels 1a, 2 and 3 in gastrointestinal mechanosensory function. Gut 2005; 54:1408-1415.
20. Page AJ, O’Donnell & Blackshaw LA. Inhibition of mechanosensitivity in visceral primary afferents by GABAB receptors involves calcium and potassium channels. Neuroscience 2006; 137(2): 627-36.
21. Slattery JA, Page AJ, Dorian C, Brierley S & Blackshaw LA. Potentiation of vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors. Journal of Physiology 2006; 577: 295-306.
22. Young RL, Page AJ, Cooper NJ & Blackshaw LA. Peripheral vs central modulation of gastric vagal pathways by mGluR5. American Journal of Physiology 2007; 292: G501-511
23. Page AJ, Slattery JA, Milte C, Laker R, O’Donnell TA, Brierley SM, Dorian CL & Blackshaw LA. Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents. American Journal of Physiology 2007; 292: G1376-1384
24. Page AJ, Brierley SM, Martin CM & Blackshaw LA. Acid sensing ion channels required for inhibition of afferent mechanosensitivity by benzamil. Pain 2007; 133: 150-160
25. Page AJ, Slattery JA, Brierley SM, Jacoby AS & Blackshaw LA. Involvement of galanin receptors 1 and 2 in the modulation of mouse vagal afferent mechanosensitivity. Journal of Physiology 2007; 583: 675-684
26. Brierley SM, Page AJ, Hughes PA, Adam, B, Liebregts T, Cooper NJ, Holtmann G, Liedtke W & Blackshaw LA. A selective role for TRPV4 ion channels in visceral sensory pathways. Gastroenterology 2008; 134: 2059-2069
27. Page AJ, O’Donnell TA & Blackshaw LA. Opioid modulation of ferret vagal afferent mechanosensitivity. American Journal of Physiology 2008; 294: G963-970
28. Page AJ, O’Donnell TA, Cooper NJ, Young RL & Blackshaw LA. Nitric oxide as an endogenous peripheral modulator of visceral sensory neuronal function. Journal of Neuroscience 2009; 29: 7246-7255.
29. Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O’Donnell TA, Cooper NJ, Harrington AM, Adam, B, Liebregts T, Holtmann G, Corey DP, Rychkov GY & Blackshaw LA. The ion channel TRPA1is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology 2009; 137: 2084-2095.
30. Lehmann A, Antonsson M, Holmberg AA, Blackshaw LA, Branden L, Brauner-Osborne H, Christiansen B, Dent J, Elebring T, Jacobson BM, Jensen J, Mattsson JP, Nilsson K, Oja SS, Page AJ, Saransaari P & von Unge S. (R)-(3-amino-2fluoropropyl) phosphonic acid (AZ3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. Journal of Pharmacology and Experimental Therapeutics 2009; 331: 504-512.
31. Young RL, Page AJ, Cooper NJ, Frisby CL & Blackshaw LA. Sensory and motor innervation of the crural diaphragm by the vagus nerves. Gastroenterology 2010; 138: 1091-1101.
32. Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY & Blackshaw LA. TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. Journal of Physiology 2011; 589: 3575-3593.
33. Kentish S, Li H, Philp LK, O’Donnell TA, Isaacs NJ, Young RL, Wittert GA, Blackshaw LA, Page AJ Diet-induced adaptation of vagal afferent function. J.Physiol 2012; 590: 209-211.
34. Kentish SJ, O’Donnell TA, Isaacs NJ, Young RL, Li H, Harrington AM, Brierley SM, Wittert GA, Blackshaw LA, Page AJ Gastric vagal afferent modulation by leptin is influenced by food intake status. J Physiol 2013; 591: 1921 -1934.
35. Kentish SJ, Wittert GA, Blackshaw LA, Page AJ. A chronic high fat diet alters the homologous and heterologous control of appetite regulating peptide receptor expression. Peptides (In press) DOI: 10.1016/j.peptides.2013.06.004.
36. Kentish SJ, O'Donnell TA, Frisby CL, Li H, Wittert GA, Page AJ. Altered gastric vagal mechanosensitivity in diet-induced obesity persists on return to a normal chow and is accompanied by increased food intake. International Journal of Obesity (In press) DOI: 10.1038/ijo.2013.138
37. Li H, . Kentish SJ, Kritas S, Young RL, Isaacs NJ, O'Donnell TA, Blackshaw LA, Wittert GA, Page AJ Modulation of murine gastric vagal afferent mechanosensitivity by neuropeptide W. Acta Physiologica 2013 (In press).
Journal Articles (Review)
1. Blackshaw LA, Page AJ, Smid S, Dent J, Lehmann A GABAB receptors – peripheral and central targets for controlling gastro-oesophageal reflux. Current Opinion in Central and Peripheral Nervous System Investigational Drugs. 2000; 2: 333-343.
2. Blackshaw LA, Page AJ & Young RL Metabotropic glutamate receptors as novel therapeutic targets on visceral afferents Frontiers in Neuroscience (Invited Review) 2011; 24: 1-7.
3. Page AJ, Symonds E, Peiris M, Blackshaw LA, Young RL Peripheral neural targets in obesity. Br J Pharmacol. 2012; 166: 1537 -1558.
1. Page AJ & Blackshaw LA The nature of esophageal pain receptors. Esophageal Pain. Ed. Dr R.K. Mittal. Plural publishing Inc. (2009) 27-39.
2. Page AJ & Blackshaw LA Roles of gastro-oesophageal afferents in the mechanisms and symptoms of reflux disease. Handbook of experimental Pharmacology: Pharmacology of Sensory Nerves. Eds Prof. D. Spina & Prof. B. Canning. Springer-Verlag Berlin Hiedelberg. (2009) 227-257.
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