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Prof Andy Ramage
Gower Street
  • Emeritus Professor of Systems Pharmacology
  • Div of Biosciences
  • Faculty of Life Sciences

In 1970 I was awarded a BSc in Physiology and Biochemistry from the University Southampton and in 1973 a M.Phil. on the effects of cholinergic and monoaminergic inputs onto identified neurones in the brain of the garden snail Helix aspersa. This led to the discovery that octopamine may be a transmitter in this system (Experientia, 28, 1173, 1972). This research was carried out under the supervision of Robert Walker. In 1972 I carried out research, although briefly (9 months), on nicotine receptors and sodium movement in snail neurones with David Brown at Bart's Pharmacology Department. In October of that year I took up a Research Fellowship in the Department of Pharmacology at the University of Manchester and completed my PhD (1977) on the effects of chemical irritants/riot gases on somatosensory receptors. This research lead to the demonstration that capsaicin and related chemicals selectively activated polymodal nociceptors and indicated that these somatosensory receptors were responsible for the cutaneous axon reflex (Neuropharmacol., 20,191-198, 1981). My supervisor was Bob Foster and Ainsley Iggo kindly showed me how to record from single C-fibres. In 1976 Prof. Eleanor Zaimis invited me to take up a lectureship in Pharmacology at the Royal Free Hospital School of Medicine to study the effects of antihypertensive drugs on the central regulatory mechanisms involved in the control of blood pressure. On her retirement in 1980 I built up my own research area in systems neuropharmacology investigating the role of monoamines, with special reference to 5-HT, in central autonomic regulation. During this period I developed a long term collaboration with David Jordan in the Physiology Department, who died prematurely in 2007. Also in 2007 I moved from the Royal Free Campus to the Pharmacology Department in the Medical Sciences Building at the Bloomsbury Campus. This department in 2009 became part of the Research Department of Neuroscience, Physiology & Pharmacology. In  2015 I became  emeritus and took up the part time position of professorial research associate in the department. 

Research Groups
Research Summary

My research has focused on trying to understanding the mechanisms involved in the modulation of chemical neurotransmission and how changes in its regulation affect the overall physiological outcome.  This has and is focussed on the central transmitter 5-hydroxytrptamine (5-HT, serotonin), with particular reference to its involvement cardiovascular system and the control of micturition.  These systems allow well defined CNS inputs to be activated, which give quantifiable outputs.  Therefore when interfering with transmission within the central nuclei involved in the integration of these inputs the physiological effect can be accurately assessed and related to changes in chemical transmission.  As an in vivo experimental approach has always been used, the overall physiological importance of such manipulations can be determined.  The use of this experimental system has led  to recognition of the importance of the role of 5-HT receptors and thus 5-HT containing neurones in central autonomic regulation. 5-HT was identified as a major central transmitter involved in the control of parasympathetic outflow to the heart, airways and bladder via activation of 5-HT1A and 5-HT7 receptors. In addition, 5-HT3 receptors were identified as also playing a critical role in the control of afferent input into the nucleus tractus solitarius involving glutamate release. Furthermore the control of sympathetic outflow was demonstrated to involve central 5-HT2 receptors which cause sympatho excitation. In addition, these receptors, via a central angiotensinergic pathway, control the release of vasopressin and this discovery led to the suggestion that this pathway plays an important role in blood volume regulation and this circuit is also involved in the development of DOCA-salt hypertension in rats. In this respect we are at present investigating the role of 5-HT7 receptors and the dorsal raphé in the development of stress hypertension. As this has been carried out using 5‑HT receptor agonists/antagonists the pharmacology of such ligands is also of major interest. Another major breakthrough using this approach has been the recognition that vagal afferents cause the release of 5-HT at their site of termination in the nucleus tractus solitarius (NTS).  As this also occurs along with the release of glutamate, the role of co-transmission in neurotransmission can be investigated in this system.  This discovery has further led to an interest in how transmitter release is controlled and the problems of studying such release in vivo and in real time.  Particularly to be able to demonstrate the role of autoreceptors modulation, along with the importance of various transporters involved in controlling the prevalence of transmitter in  the synapse.  Intriguingly this has open up an interest into the role of glia cells in chemical transmission and to whether volume transmission can be demonstrated.

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