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Research Summary

In the field of pharmacology, we are divided into three large research groups: neuropharmacology, cardiovascular pharmacology and clinical pharmacology. Research on neuropharmacology newly started in 1997 when Professor Hiroshi Higuchi arrived at our department, and research on cardiovascular pharmacology has been ongoing since the time when former Professor Shoichi Imai was in the department. While these may seem to be quite different areas, they are interrelated in many ways, and these two areas of research are now conducted in parallel. Clinical pharmacology aims to broadly deliver the data obtained with analytical techniques to clinical medicine at the individual and organ levels. It strives to make use of specialist experience in pharmacology for developing clinical drug therapy. We are mainly introducing the research summary of neuropharmacology and cardiovascular pharmacology conducted by our department during the last 7 years.

First, we introduce neuropharmacology research. In recent years, neuroscience has advanced remarkably, and it can now be said that the mechanisms of brain functions such as memory, learning, emotion, desire and thought, which were considered to be difficult to understand, are emerging though only vaguely. Our research focus is to clarify the genes which constitute hereditary factors involved in diseases and their roles in the living body, and to make the mechanism of gene transcription as the site of action of drugs clear based on the above understanding. Specifically, our current research can be delineated as follows:

Expression regulation mechanism of neural-specific genes involved in neural transmission

We conduct research on the transcription regulation mechanism of neural-specific genes involved in neural transmission, focusing on the gene expression of neuropeptide Y, one of the neuropeptides, and enkephalin. In particular, we conduct research to determine which transcription factors regulate the transcription of neural-specific genes. We are clarifying that these transcription factors are potential sites of action for drugs.

Identification and analysis of new transcription factor group involved in neuron differentiation including the sympathetic nerve

(Approach to neuron differentiation)

For this research, we perform in vivo analysis by introducing zebrafish, a sensitive experimental animal which allows direct experiments, for the analysis of transcription factors.

Transcription regulation by neural-specific signals (Approach to memory and neuroplasticity)

We conduct research on the transcription regulation mechanism of neural genes, focusing on the molecular mechanisms of neurotrophic factors such as nerve growth factors (NGF) which are critical for nerve cell differentiation and survival (approach to brain aging).

Molecular pharmacology of neuropeptide receptors

Approximately 40 types of neuropeptides have been identified to date, but there are very few whose physiological function has been clarified. However, it is clear that neuropeptides play important roles in central nervous system functions including emotion and sense, as illustrated by many examples, and there is no doubt that studies of neuropeptides will become important research areas in the future. Clarification of the signal information transfer mechanisms of various neuropeptide receptors on the molecular level is essential for clarification of the physiological functions of neuropeptides and for the development of specific agonists and antagonists, which may lead to the development of drugs for treating disorders of higher mental function, such as anti-dementia drugs, in the future.

Next, we introduce research on cardiovascular pharmacology. The main research project when Professor Imai was in our department was the mechanism of action of nitroglycerine which exerts a potent vasodilating action and is used as a specific treatment for angina. The vasodilating action of nitroglycerine occurs via an increased level of the substance called cyclic GMP after it is converted to nitric oxide (NO) in the blood vessel. This means that the mechanism of action of nitroglycerine is directly related to the newly-recognized physiologically active agent NO, which was the research subject of the winner of the Nobel Prize in Medicine last year. We have conducted research mainly on the mechanism of the vasodilating action of nitroglycerine after it is converted to NO. We have conducted many studies on the role of G kinase, a protein phosphorylation enzyme activated by cyclic GMP, and the identification of matrix protein, the mechanism of a decrease in calcium sensitivity of contractile protein of smooth muscle, the difference in reactivity to nitroglycerine of the thick and thin parts of the coronary artery, etc. In addition, as the research projects we have newly started, we can mention our pathophysiological research on experimental autoimmune myocarditis in rats, research on the physiology of neuropeptide Y in the circulatory system, fundamental research on gene therapy using hereditary myocarditis model animals, etc.