Histamine-sensitive adenylate cyclase in mammalian brain.

Abstract

THERE is increasing interest in the possibility that histamine may be a neurotransmitter in the mammalian central nervous system (CNS). Electrophysiological evidence supports the existence of histamine receptors in nervous tissue through which neuronal excitability can be regulated. For example, the firing rate of certain neurones in the brain is depressed by histamine and this depression is specifically blocked by the H2 antagonist, metiamide1. In addition, histamine influences the electrical excitability of neurones in the superior cervical ganglion2. Certain neurotransmitters may exert some of their effects in nervous tissue by stimulating the formation of cyclic AMP. It is therefore of interest that histamine raises cyclic AMP levels in brain slices3–7, as do several other putative neurotransmitters, such as noradrenaline, dopamine and 5-hydroxytryptamine (5-HT). Furthermore, a dopamine-sensitive adenylate cyclase has been found in homogenates of rat caudate nucleus and olfactory tubercle, with properties very similar to those of the dopamine receptor in mammalian brain8–10. We report here the occurrence of an adenylate cyclase which is activated by low concentrations of histamine in several regions of guinea pig brain. This histamine-sensitive adenylate cyclase has the pharmacological properties of an H2 receptor. The results indicate that the actions of histamine on H2 receptors in the CNS may be mediated through cyclic AMP.