Cerebral Histamine: Indications for Neuronal and Vascular Regulation

Seventy-two years ago, Sir Henry Dale discov­ ered that histamine (8-iminazolylethylamine) was a constituent of most mammalian tissues and was a potent agonist on a variety of biological target cells (Dale and Laidlaw, 1910; Dale, 1953). It was suggested that this amine may have a transmitter role in several organs, conveying messages from cells where it was synthesized or stored to adjacent cells that responded to its presence. Several criteria need to be met, however, to establish a candidate transmitter substance as a chemical messenger. In the brain, this task is made more difficult due to the inherent heterogeneity and complexity of cerebral anatomy and function. In the past decade, signifi­ cant advances have been made in understanding how histamine affects cerebral processes (Reviews: Monnier et aI., 1970; Snyder and Taylor, 1972; Cal­ cutt, 1976; Schwartz et aI. , 1976; Schwartz, 1977; Green et aI. , 1978, 1979; Schwartz, 1979; Schwartz et aI., 1979; Garbarg et aI. , 1980a; Schwartz et aI. , 1980a,b). Furthermore, there is now convincing evidence that a number of psychotropic drugs may interact with cerebral histamine receptors (Kanof and Greengard, 1978; Chang et aI. , 1979; Quach et aI. , 1979; Green et aI. , 1980; Diffley et aI. , 1980; Taylor and Richelson, 1980). Some mental disor­ ders may, therefore, involve disturbances of brain histamine metabolism (Green et aI. , 1978, 1979). Historically, histamine has been of experimental interest because of its potent effects on vascular function, especially in pathological conditions such as traumatic injury, inflammation, and hypersen­ sitivity reactions (Beaven, 1978; Plaut, 1979). Al­ though these processes alone emphasize a need to