Studies on histamine-induced cutaneous flare in the guinea pig.

Evidence for the involvement of both H1- and H2-receptors in histamine-induced cutaneous flare reactions has been obtained. The guinea pig ear was used as the site of histamine injection since, unlike virtually all other skin areas in non-humans examined to date, it displays a similar response to that which occurs in human skin, namely the Lewis triple response. The flare reaction to histamine in the guinea pig ear was established as an indirectly mediated, neurovascular phenomenon by demonstrating that the vascular changes which occur in the region of the flare are incompatible with histamine directly stimulating the cutaneous vasculature and also by showing that histamine-induced cutaneous flare reactions are reduced by local anaesthesia. Having verified the authenticity of the flare reaction in the guinea pig ear, the role of H1- and H2-receptors in histamine-induced flare reactions was examined. Mepyramine and Cimetidine both significantly reduced the flare reaction produced by histamine. In addition, 2-(2-aminoethyl) pyridine, a selective H1-receptor agonist, was found to elicit a dose-dependent flare response.