Mechanisms by Which Histamine Stimulates ACTH Release in Rats

Abstract

In normal male rats lightly anesthetized with Nembutal and sodium barbital, subcut. histamine acid phosphate (10 mg./kg.) induced a 40% depression in the eosinophil count at 1 hr. The depression was prevented not only by the potent adrenergic blocking agent SKF-501 (N[9-Fluorenyl]-N ethyl- [beta]-chlorethylamine) but also by 2-dibenzyl-aminoethanol (D-ol), a Dibenamine analogue lacking adrenergic blocking properties. The latter agent, while failing to prevent epinephrine-indiced eosinopenia, is effective against non-specific stressing agents presumably by inhibiting the reflex discharge of epinephrine from the adrenal medulla. In anesthetized demedullated rats, subcut. histamine failed to lower the 1-hr. eosinophil count. Intraven. histamine, on the other hand, in combination with a subcut. dose is effective in inducing eosinopenia even in anesthetized, demedullated animals, and the response is not blocked by D-ol. The results indicate that subcut. histamine acts as a non-specific stressing agent whose effect on the hypophysis is mediated at least in part via the adrenal medulla, whereas intraven. histamine may act directly upon the hypophysis.