Development of a new in vivo anaphylactic histamine release assay in rats.

A new method has been developed to detect antigen-induced histamine release in the blood of allergic rats. This in vivo model of systemic anaphylaxis has been utilized to evaluate drugs for histamine release inhibition activity. Compounds were administered by various routes at appropriate times prior to or concomitant with antigen challenge. One minute after challenge the rats were bled into tubes containing heparin and aminoguanidine. Histamine concentrations were determined by a radioenzyme technique after separation of the plasma. Experiments demonstrated that: (a) rats passively sensitized with reaginic serum exhibited elevated blood histamine upon i.v. antigen challenge in a reproducible and dose-dependent manner; (b) heat-treatment of the reaginic serum abolishes antigen-induced histamine release; and (c) antigen-induced histamine release is inhibited by disodium cromoglycate, in a dose-dependent manner and it is also inhibited by isoproterenol or isobutyl-methylxanthine.