Studies on the Functional Role of Adenosine 3', 5'-monophosphate, Histamine and Prosta Glandin E₁ in the Central Nervous System

A wide variety of hormones, such as epinephrine, glucagon and ACTH, increase the intracellular concentration of cyclic AMP in several tissues and cyclic AMP induces simi lar effects to those of many hormones (1, 2). Thus it has been proposed that cyclic AMP mediates the responses of these hormones. Increased concentrations of cyclic AMP in tissues are caused by enhanced adenyl cyclase activity or suppressed phosphodiesterase activity. The activities of these enzymes are known to be higher in the brain than in other tissues (3, 4). Cyclic AMP was previously reported by Siggins, Hoffer and Bloom (5) to interfere with neuronal activity in the cerebellum of rats. It is conceivable that cyclic AMP may play a role in regulating the activities of the cells of central nervous system as an intracellular mediator of responses to transmitters and hormone-like compounds. In support of this Kakiuchi and Rall (6) reported that on incubation of slices of rabbit cere bral cortex with histamine a large amount of cyclic AMP accumulated in the slices. Re cently similar results were reported by other investigators (7-9). Kwiatkowski (10) first found histamine in various areas of the central nervous system and subsequently his findings have mostly been confirmed (11-15). However, little is known about the function of histamine in the central nervous system. Prostaglandins have been found to be present in the brain, as in other tissues, of sever al species (16-24) and these compounds are widely distributed throughout all regions of the brain (24). Horton (25) observed that intraventricular administration of PGE, to cats caused sedation and stupor. Spontaneous movement of the cat decreased and the cat lost interest in its surroundings. In adipose tissue and toad bladder, prostaglandin E was reported to inhibit the responses to lipolytic hormones and vasopressin, and this inhibition was attributed to inhibition of the activation of adenyl cyclase by these hormones (26-31). It is also possible that prostaglandin E may be involved in regulation of the intracellular concentration of cyclic AMP in the central nervous system. These observations suggest that cyclic AMP, histamine and prostaglandin E are all