Prostaglandins and sleep.

The concept of humoral regulation of sleep was initially proposed by a French neuroscientist, Henri Piéron of Paris, in the first decade of this century. He and his associate Legendre were the first to show the presence of a sleep-inducing substance in the cerebrospinal fluid (CSF) of sleep-deprived dogs. Concurrently and independently, Kuniomi Ishimori of Nagoya University, Nagoya, Japan, employing a similar experimental approach, also demonstrated a sleep-inducing substance in the CSF of sleep-deprived dogs. During the next 80 years or so, more than 30 so-called endogenous sleep substances have been reported to exist in the brain by numerous investigators, CSF, and other organs and tissues of mammals. However, their physiological relevance has remained uncertain in most instances. In this review, we shall focus upon our own work concerning the molecular mechanisms of sleep-wake regulation by prostaglandins (PGs) D2 and E2, with special emphasis on the recent developments during the last several years.