Action of histamine receptor agonists and antagonists on the rat uterus.
1 Histamine and a series of compounds acting selectively on H1- 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 greater than histamine greater than N'-N'-dimethylhistamine greater than 5-methylhistamine greater than 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.
D000818:Animals; D002369:Castration; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D051381:Rats; D011968:Receptors, Histamine / Q000187:drug effects*; D013045:Species Specificity; D014590:Uterine Contraction / Q000187:drug effects*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D011968:Receptors, Histamine