Inhibition of Histamine Release by Histamine controlled by H2 Receptor

Abstract

AGENTS which increase the intracellular level of adenosine 3′-5′-monophosphate (cyclic AMP) in human leukocyte preparations such as the catecholamines, methylxanthines and prostaglandins, inhibit the antigen induced, IgE antibody mediated release of histamine from human leukocytes (basophils)^1–3. Not only are the dose response relationships for increased cyclic AMP levels and the inhibition of histamine release similar, but the kinetics of the two events are also parallel and it is accepted as a working hypothesis that changes in the cyclic AMP level of human basophils (and mast cells) modulate the in vitro allergic response^4–6. Recently, we showed that exogenous histamine could increase the cyclic AMP level of human leukocyte preparations and stop the release of endogenous histamine. This occurred at concentrations of histamine (about 10⁻⁶ M) which are present in the cell suspension under study⁷. For this reason we suggested that histamine could “feedback” to control the spread of an allergic response by decreasing the response of other target cells (tissue mast cells, blood basophils) to an allergenic challenge. No clear effect of antihistamines on the inhibition of histamine release by histamine was observed: concentrations up to 10⁻³ M to 10⁻⁴ M of several antihistamines had little effect and higher concentrations of these drugs either caused inhibition of histamine release themselves or were cytotoxic_2,7.