Pharmacological investigations into the effects of histamine and histamine analogs on guinea pig and rat uterus

Abstract

The effects of histamine and its analogs 2-(2-pyridyl) ethylamine (PEA) and 4-methylhistamine (4 MH) have been studied on uterine preparations obtained from estrogen-primed guinea pigs and rats. (1) Histamine and 4 MH, a specific H2-receptor agonist produced relaxation in estrogen-primed rat uterus, whereas these agonists produced contraction in the estrogen-primed guinea pig uterus. (2) PEA, a specific H1-receptor agonist produced contraction in the guinea pig uterus but had no effect on the rat uterus. (3) Metiamide blocked responses to histamine and 4 MH in the rat uterus, whereas mepyramine blocked responses to histamine and PEA in the guinea pig uterus. (4) Propranolol produced competitive antagonism with histamine in the rat uterus, whereas it had no significant effect on the histamine or PEA responses in the guinea pig uterus. (5) Reserpine pretreatment completely abolished the responses to histamine and 4 MH in the rat uterus but did not alter the response in the guinea pig uterus. (6) Our data suggest that in rat uterus only H2-receptors are present and they are indirectly through the release of noradrenaline. In the guinea pig uterus both H1- and H2-receptors are present and are excitatory and directly acting.

Effect of histamine and histamine analogues on human isolated myometrial strips

“…This finding agrees with previous results in various tissues, including the guinea-pig isolated uterus, although in this latter study 2-pyridylethylamine was shown to be less potent than histamine (Duncan et al, 1980;Goyal & Verma, 1981;Schmidt et al, 1987). The contractile effect of 4-methylhistamine agrees with a similar result in guinea-pig uterus and confirms previous findings were 4-methylhistamine was a histamine H1-agonist (Goyal & Verma, 1981;Black et al, 1972). This underlines the importance of the numbers of histamine HI-: histamine H2-receptors in a tissue for the observed effect of agonists which are not very selective (Barker & Hough, 1983 Moreover, dimaprit and 4-methylhistamine (in the presence of HI-blockade) also produced a similar relaxant effect.…”

“…Although 2-pyridylethylamine appears to be a partial agonist (Figure 1), paired experiments showed that the maximal effects of both compounds were similar. This finding agrees with previous results in various tissues, including the guinea-pig isolated uterus, although in this latter study 2-pyridylethylamine was shown to be less potent than histamine (Duncan et al, 1980;Goyal & Verma, 1981;Schmidt et al, 1987). The contractile effect of 4-methylhistamine agrees with a similar result in guinea-pig uterus and confirms previous findings were 4-methylhistamine was a histamine H1-agonist (Goyal & Verma, 1981;Black et al, 1972).…”

“…However, after blockade of histamine H1-receptors, histamine produced a slight inhibitory effect in strips precontracted by KCI. The contractile effect of histamine observed in this study resembles that described by Goyal & Verma (1981) in guinea-pig isolated uterus, where histamine produced a dose-related contraction with a similar potency. Our results also confirmed those described by Farmer & Lehrer (1966) in human isolated myometrium, although a comparative analysis of the findings is difficult because the authors did not give the details of their experimental procedure and used only single doses of histamine.…”

“…Thus, histamine produces contractions of guinea-pig uterine horns, but causes relaxation of the rat uterus. The receptors involved in these two effects are classified as histamine Hr-and H2-receptors respectively (Black et al, 1972;Tozzi, 1973;Goyal & Verma, 1981;Rubio et al, 1982;Cortijo et al, 1984). However, there is little information on the effect of histamine on the human uterus, and previous studies reported in the literature have come to differing conclusions.…”

IgE-Independent Mast Cell Activation Augments Contractility of Nonpregnant and Pregnant Guinea Pig Myometrium

“…Some of the mast cell mediators by themselves can stimulate uterine smooth muscle contractility. It has been reported that histamine, serotonin, PGF 2 α , thromboxane A 2 mimetic (U46619), LTC 4 and LTD 4 , and PDE 2 stimulate contractility in isolated myometrium from human, guinea pig, mice and rat myometrium, as well as in the guinea pig cervix [5,6,7,8,9,10,11,12,13,14,15,16,17]. …”