Tohoku J. Exp. Med., 2001, 195 (4)

Review

Studies on Functional Roles of the Histaminergic Neuron System by Using Pharmacological Agents, Knockout Mice and Positron Emission Tomography

TAKEHIKO WATANABE and KAZUHIKO YANAI

Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575

Since one of us, Takehiko Watanabe (TW), elucidated the location and distribution of the histaminergic neuron system in the brain with antibody raised against L-histidine decarboxylase (a histamine-forming enzyme, HDC) as a marker in 1984 and came to Tohoku University School of Medicine in Sendai, we have been collaborating on the functions of this neuron system by using pharmacological agents, knockout mice of the histamine-related genes, and, in some cases, positron emission tomography (PET). Many of our graduate students and colleagues have been actively involved in histamine research since 1985. Our extensive studies have clarified some of the functions of histamine neurons using methods from molecular techniques to non-invasive human PET imaging. Histamine neurons are involved in many brain functions, such as spontaneous locomotion, arousal in wake-sleep cycle, appetite control, seizures, learning and memory, aggressive behavior and emotion. Particularly, the histaminergic neuron system is one of the most important neuron systems to maintain and stimulate wakefulness. Histamine also functions as a bioprotection system against various noxious and unfavorable stimuli (for examples, convulsion, nociception, drug sensitization, ischemic lesions, and stress). Although activators of histamine neurons have not been clinically available until now, we would like to point out that the activation of the histaminergic neuron system is important to maintain mental health. Here, we summarize the newly-discovered functions of histamine neurons mainly on the basis of results from our research groups.

Keywords —— histamine; histidine decarboxylase; pharmacology; brain; knockout mouse; PET

© 2001 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2001, 195, 197-217

Address for reprints: Kazuhiko Yanai, Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.

e-mail: yanai@mail.cc.tohoku.ac.jp

This review is partly based on the Special Lecture given by TW at the 74th Annual Meeting of the Japanese Pharmacological Society on March 25, 2001 at Yokohama (Folia Jap. Pharmacol. Soc., 118[3], 159-169 [2001] [in Japanese]), and summarizes the studies carried out in our hands with no aim to cover all the related literature. This review was written to commemorate the retirement of TW on March 31, 2002 and the 3rd anniversary of professorship of KY.