ACTION OF HISTAMINE RECEPTOR AGONISTS AND ANTAGONISTS ON THE RAT UTERUS

Abstract

Histamine and a series of compounds acting selectively on H r and H 2 ‐receptors were tested on the isolated oestrous uterus of the rat. Histamine had a dose‐dependent inhibitory effect on the contractions elicited by acetylcholine. This action was unaffected by H 1 ‐blockers but was competitively inhibited by H 2 ‐blockers. The H 1 ‐selective agonist, 2‐(2‐aminoethyl)thiazole was ineffective at doses 100 times greater than those of histamine. Conversely, all the H 2 ‐agonists showed activity in the order of potency: N' ‐methylhistamine > histamine > N'‐N' ‐dimethylhistamine > 5‐methylhistamine > 5‐methyl‐ N' ‐methylhistamine. Among the non‐imidazole compounds, dimaprit had an activity identical to that of histamine, but all the dimaprit‐like compounds showed negligible activity. The data obtained suggest that in the rat uterus, (a) the activation of H 2 ‐receptors is responsible for the inhibitory effect of histamine and its analogues; (b) the integrity of the histamine molecule seems to be less crucial than that of the dimaprit molecule for the maintenance of the H 2 ‐activity, since changes in its structure modify but do not abolish the biological activity as they do in the case of dimaprit; (c) the order of activity of the various H 2 ‐receptor agonists is different from that observed in other tissues.