Signal transduction by histamine in the cerebellum and its modulation by N-methyltransferase

Histamine has been suggested to have roles as a neurotransmitter or a neuromodulator. Direct fiber connections between the hypothalamus and the cerebellum have recently been demonstrated and it is suggested that the cerebellum is involved in the control of autonomic and emotional functions. These fibers include histaminergic fibers. The components of histaminergic signal transmission are demonstrated in the cerebellum as follows: (1) the histaminergic fibers are visualized immunohistochemically in the cerebellar cortex of rat, guinea pig and human; (2) histamine H1 receptors are visualized by autoradiographic studies in the molecular layer of mouse and guinea pig. In situ hybridization study also detects the expression of H1 receptors in the Purkinje cells. H2 receptors are expressed in the Purkinje cells and granule cells of guinea pig; and (3) the application of histamine to the slices of guinea pig or rat cerebellar cortex elicits an increase in the turnover of phosphoinositides, so H1 receptors in the cerebellum are functional. Additionally, we have recently shown in the guinea pig that Purkinje cells express one of the histamine inactivating enzymes, and that inhibition of this enzyme enhances phosphoinositide turnover by histamine. Therefore, all the components of histaminergic neurotransmission are demonstrated in the cerebellum. These data suggest that histamine is involved in the signal transmission from the hypothalamus to the cerebellum. Here we review each component of histaminergic neurotransmission in the cerebellum.