Relations between the effects of histamine, pheniramin and metiamide on spontaneous motility and the formation of cyclic AMP in the isolated 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 > 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.

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“…Dashed lines indicate 95x' confidence limits. Black et al (1972) and of Mitznegg, Schubert & Fuchs (1975).…”

Section: Discussionmentioning

confidence: 97%

Action of Histamine Receptor Agonists and Antagonists on the Rat Uterus

Bertaccini

Molina

Vitali

et al. 1979

British J Pharmacology

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“…Since the mechanical and the biochemical responses to histamine were found to be prevented by H2-receptor antagonists on gastric mucosa [22,23] as well as on uterus smooth muscle [24], these effects were thought to be due to stimulation of H2-receptors. Since the mechanical and the biochemical responses to histamine were found to be prevented by H2-receptor antagonists on gastric mucosa [22,23] as well as on uterus smooth muscle [24], these effects were thought to be due to stimulation of H2-receptors.…”

Section: Discussionmentioning

confidence: 99%

H1- and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts

Reinhardt¹,

Schmidt²,

Brodde³

et al. 1977

Agents and Actions

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On guinea-pig heart we investigated whether cyclic AMP serves as a messenger for H1 - and/or H2-mediated responses to histamine. (1) On papillary muscle histamine elicited positive inotropic responses which were antagonized by burimamide but not by promethazine. The stimulation of H2-receptors was not only associated with an increase in contractility but also with an increase in cAMP. As shown by the time course of effects for 10(-5) M histamine, the maximal increase in cAMP preceded the maximum in contractility. The mechanical and biochemical responses to histamine were potentiated by the phosphodiesterase inhibitor papaverine, but antagonized by burimamide. (2) On the left guinea-pig atrium containing H1-receptors the inotropic response to histamine (10(-5) M) was not accompanied by increases in cAMP at stimulation frequencies of 0.5 and 2 Hz, respectively. In addition, in the presence of papaverine (3 X 10 (-5) M) no change in the cyclic AMP level occurred after application of histamine. Papaverine by itself, however, concomitantly increased contractility and cyclic AMP at a stimulation frequency of 0.5 Hz. In contrast, at 2 Hz papaverine increased only cAMP leaving the contractility unchanged. At this frequency the well-known Ca2+-antagonistic effect comes into prominence, thus masking the positive inotropic effect attributable to the inhibition of the phosphodiesterase. (3) On the right guinea-pig atrium the mediation of the positive chronotropic response to histamine by H2-receptors which is partly involved in the inotropic effect via the frequency-force relationship does not lead to a concomitant increase in cAMP. Also, in the presence of papaverine, histamine had no influence on the cAMP. However, papaverine potentiated the cardioacceleration produced by histamine. Although it is very likely that the cAMP in the sinus node rises, we were not able to detect an increase in cAMP in the whole atrial tissue. From the present results the conclusion can be drawn that the mediation of the inotropic effect due to stimulation of H2-receptors by histamine is associated with an increase of cyclic AMP, whereas that of H1-receptors is not. The view that cAMP may be the second messenger in the chronotropic action of histamine needs further elucidation by experiments on sino-atrial cells.

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“…In addition, relaxin causes uterine relaxation, both in vivo (Feiton, Frieden & Bryant, 1953;Porter, Downing & Bradshaw, 1979) and in vitro (Griss, Keck, Engelhorn & Tuppy, 1967). Myometrial relaxation induced by ß-adrenoceptor agonists (Johansson & Andersson, 1978) and histamine (Nitznegg, Schubert & Fuchs, 1975) are associated with an increase in the tissue concentration of cyclic AMP. We therefore examined the postulate that myometrial relaxation produced by relaxin may be linked to activation of adenylate cyclase and formation of cyclic AMP.…”

Section: Introductionmentioning

confidence: 96%

Modulation of Cyclic Amp in Isolated Rat Uterine Tissue Slices by Porcine Relaxin

Judson¹,

Pay²,

Bhoola³

1980

Journal of Endocrinology

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Porcine relaxin produced a rapid, dose-related rise of cyclic AMP values in rat uterine tissue incubated in vitro. In time-course experiments, peak cyclic AMP concentrations were observed in the uterine slices at 5 min; subsequently the values fell, at first rapidly and then more slowly with the tissue concentration remaining significantly raised at 15 min. Levels of cyclic GMP in the same tissue slices were not significantly altered by relaxin. Furthermore, no increase in basal cyclic AMP values was measured in control slices prepared from the rat heart or jejunum. An increase in cyclic AMP concentration comparable to that found in the rat uterus was observed in slices of porcine uterus and cervix but not of vagina when they were stimulated with porcine relaxin. Our results suggest that the hormonal action of relaxin on the uterus and cervix is mediated through receptors linked to the enzyme, adenylate cyclase.

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Relations between the effects of histamine, pheniramin and metiamide on spontaneous motility and the formation of cyclic AMP in the isolated rat uterus

Cited by 13 publications

References 15 publications

Action of Histamine Receptor Agonists and Antagonists on the Rat Uterus

Action of Histamine Receptor Agonists and Antagonists on the Rat Uterus

H1- and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts

Modulation of Cyclic Amp in Isolated Rat Uterine Tissue Slices by Porcine Relaxin

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