Rat jejunal mucosal response to histamine and anti-histaminesin vitro. Comparison with antigen-induced changes during intestinal anaphylaxis

We previously showed that rats sensitized to egg albumin (EA) respond toin vivo intraluminal antigen-challenge with decreased net absorption of water and electrolytes and depletion of mucosal histamine. However, administration of anti-histamines did not prevent the transport abnormalities. The presentin vitro studies examined the effect of histamine to alter net ion transport and the ability of diphenhydramine (DPH) and cimetidine (CIM) to block the responses to both histamine and antigen. Control rat jejunum was mounted in Ussing chambers and histamine was added to the serosal side either in the absence or presence of DPH or CIM. In control tissues histamine caused a transient increase in short-circuit current (Isc) in a dose-dependent manner between 10−5 and 10−4 M which was blocked by 10−5 M DPH but was unaffected by CIM in concentrations up to 10−4 M. There was no response to EA. Jejunum from sensitized rats exposed to EA demonstrated a biphasic Isc response: a rapid transient rise followed by a somewhat less elevated but sustained component. In tissues pre-treated with DPH the initial peak Isc response was significantly reduced. In the presence of the neurotoxin, tetrodotoxin, the initial peak was unaffected but the sustained component was reduced. Our results indicate that H1-receptors mediated the effects of histamine in rat jejunal mucosa but that during intestinal anaphylaxis histamine is responsible for only a portion of the antigen-induced transport abnormalities. Our data also suggest that IgE-mediated reactions in the intestine may involve an interaction between mast cell mediators and enteric nerves.