On the interaction between H1- and H2-histaminergic receptors in the histamine release and the realization of its vascular effects in rat skin.

The influence of the H1- and H2-histaminergic blockers promethazine and cimetidine, respectively, as well as of a combination of both drugs on the histamine release from rat ear skin, induced by compound 48/80, was studied. Cimetidine did not interfere with the effects of comp. 48/80, while promethazine increased almost three times the histamine-releasing effects of comp. 48/80. This effect of promethazine was reduced when the latter was combined with cimetidine. Cimetidine and promethazine did not produce any per se effect on the histamine content of the ear skin tissue. The two histaminergic blockers antagonized the vasodilation induced by exogenous histamine injected intradermally, the combination of the drugs in the higher dose used being most efficient. The effect of the combination was more pronounced as compared to that of promethazine when applied alone in the corresponding dose (25 mg/kg) and was almost equal to the effect of cimetidine administered alone in a dose of 200 mg/kg. The results suggest an important role for H2-histaminergic receptors in the skin vessels of rat as well as in the prevention of the mast cell degranulation at least in cases when it is induced by comp. 48/80.