ACTION OF HISTAMINE RECEPTOR AGONISTS AND ANTAGONISTS ON THE RAT UTERUS

Abstract

1 Histamine and a series of compounds acting selectively on H_r and H₂-receptors were tested on the isolated oestrous uterus of the rat. 2 Histamine had a dose-dependent inhibitory effect on the contractions elicited by acetylcholine. This action was unaffected by H₁-blockers but was competitively inhibited by H₂-blockers. The H₁-selective agonist, 2-(2-aminoethyl)thiazole was ineffective at doses 100 times greater than those of histamine. Conversely, all the H₂-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. 3 The data obtained suggest that in the rat uterus, (a) the activation of H₂-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 H₂-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 H₂-receptor agonists is different from that observed in other tissues.