In vivo inhibition of the human non-pregnant uterus by prostaglandin E2

Toppozada, M.; Gaafar, Alaa; Shaala, S.

doi:10.1016/0090-6980(74)90118-x

Cited by 21 publications

(4 citation statements)

References 9 publications

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“…In non-pregnant human myometrium in vivo early work has shown a potent stimulatory effect after intravenous, intramuscular or subcutaneous administration of PGE2 (Karim et al, 1971) which originally suggested that a discrepancy existed between the effect of PGE2 on the non-pregnant myometrium in vitro as compared to in vivo. However, later work demonstrated an inhibitory effect after intrauterine administration of PGE2 (Toppozada et al, 1974) which coincides with in vitro results. We have previously reported a biphasic response with PGE2 in the spontaneously active human myometrium in vitro (Clayton et al, 1986a).…”

Section: Introductionsupporting

confidence: 79%

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In vitro characterization of prostanoid EP‐receptors in the non‐pregnant human myometrium

Senior

Marshall

Sangha

et al. 1991

British J Pharmacology

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Postgraduate Studies in Pharmacology, University of Bradford, Bradford, BD7 lDP and *The Royal Infirmary, Bradford, BD9 6RJ1 Prostaglandin receptors of the PGE type have been characterized in the non-pregnant human myometrium in vitro according to the scheme of Coleman et al. (1984) by use of the agonists PGE2, sulprostone, rioprostil, AY23626, butaprost, misoprostol, 16,16-dimethylprostaglandin E2, enprostil and iloprost, and, the antagonist AH6809. 2 All prostanoids tested were active in non-pregnant human myometrium either as stimulators and/or inhibitors of spontaneous activity or both. Biphasic responses to PGE2 indicate that at least two receptor types of the EP-receptor exist, one mediating relaxation and the other mediating contraction. 3 Further evidence for the EP-receptor mediating excitation and relaxation was provided by the action of the EP2-/EP3-receptor selective prostanoids rioprostil, AY23626 and misoprostol, and the EP1-/EP2-receptor selective agonist 16,16-dimethylprostaglandin E2. 4 Butaprost, an EP2-receptor selective agonist, produced potent inhibition of spontaneous activity in the tissue which was generally longer-lasting than that evoked by the natural prostanoid PGE2. 5 The EP1-/EP3-receptor selective agonist sulprostone and the EP3-receptor agonist enprostil produced potent contractile responses supporting the presence of contractile EP3-receptors in the non-pregnant human myometrium in vitro.6 The EP,-/IP-receptor selective agonist, iloprost, produced mixed responses in non-pregnant human myometrium. The contractile response was inhibited by the EP,-receptor antagonist AH6809. However, responses to the EP1-/EP3-receptor selective agonist sulprostone were unaffected by AH6809 which may indicate that only a small population of EP1-receptors is present.

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Section: Introductionsupporting

confidence: 79%

“…However, later work demonstrated an inhibitory effect after intrauterine administration of PGE2 (Toppozada et al, 1974) which coincides with in vitro results. We have previously reported a biphasic response with PGE2 in the spontaneously active human myometrium in vitro (Clayton et al, 1986a).…”

Section: Introductionmentioning

confidence: 94%

In vitro characterization of prostanoid EP‐receptors in the non‐pregnant human myometrium

Senior

Marshall

Sangha

et al. 1991

British J Pharmacology

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“…Intrauterine administration of PGE2 in nonpregnant women may occasionally re sult in inhibition of the contractility [11][12][13], However, irrespective of these observations it might be questioned whether the contrac tile response induced by large doses of PGs as administered systematically reflect 'their physiological action' on the myometrium. It is possible that intracellularly synthesized and released concentrations of PGs possess local contractile effects that are different.…”

Section: Discussionmentioning

confidence: 99%

Myometrial Response to Prostaglandins during Labor

Wikland

Lindblom

Wiqvist

1984

Gynecol Obstet Invest

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The myometrial response to prostaglandins (PGs) before labor has been studied earlier in this laboratory by the use of a superfusion technique. In the present investigation the same technique was used to explore the contractile effect of PGE₂ and PGF₂_Α on myometrial strips obtained during active, spontaneous labor. Both PGE₂ and PGF_2Α had a marked stimulatory effect on strips from the upper uterine segment. The lower segment reacted to PGE₂ by inhibition but not at all or slightly stimulatory to PGF_2Α Oxytocin constantly induced an excitatory response in both segments The results support the concept of a prostaglandin-mediated ‘fundal dominance’ during labor and indicate that PGs contribute to a relaxation of the lower uterine segment. Taken together with previously obtained data the present results provide evidence for a critical change in myometrial responsiveness to prostaglandins by the time of parturition.

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“…also generally agreed that in most cases PGE2 has a stimulatory effect during the early proliferative and late secretory phases of the menstrual cycle. While we observed that the uterus was insensitive to prostaglandin around ovulation time, Toppozada et al (17,18) found an inhibitory effect of PGE2 if high doses ( 1 00-300 pg) were given by the intrauterine route. A change from stimulation to inhibition of uterine contractility in vivo has earlier been reported by Eliasson and Posse (4) following vaginal administration of a crude prostaglandin preparation, not, however, by increasing the dose, but by increasing the sensitivity of the myometrium by the addition of an intravenous infusion of a mixture of vasopressin and oxytocin.…”

Section: Discussionmentioning

confidence: 46%

Effects of the Prostaglandins on the Uterus

Bygdeman

Bremme

Gillespie

et al. 1979

Acta Obstet Gynecol Scand

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The effect of intravenous and intrauterine administration of PGEl or PGE2 and P G F Z~ as well as oral administration of PGE2 on the sensitivity and reactivity of the nonpregnant human uterus was studied. With the use of the flaccid microballoon technique or a micro transducer catheter, uterine recordings were made at frequent intervals throughout the menstrual cycle. Independently of the route of administration and of the phase of the cycle, treatment with P G F z~ invariably resulted in stimulation of uterine motility. A high sensitivity t o PGFza was noted during the late secretory phase both in normal and dysmenorrheic women.A marked decrease in sensitivity to both PGE2 and PGF2u administered by the intrauterine route was observed in the periovulatory phase. Inhibition of uterine contractility by PGE2 following both intrauterine and oral administration was noted during active menstrual bleeding in normal as well as in dysmenorrheic women.These findings suggest that endogenous prostaglandins may play a role in the regulation of the normal uterine motility during the menstrual cycle and that the main reason for the abnormal contractility pattern seen in dysmenorrheic women during menstrual bleeding is an increased PGF2,/PGE2 ratio.

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In vivo inhibition of the human non-pregnant uterus by prostaglandin E2

Cited by 21 publications

References 9 publications

In vitro characterization of prostanoid EP‐receptors in the non‐pregnant human myometrium

In vitro characterization of prostanoid EP‐receptors in the non‐pregnant human myometrium

Myometrial Response to Prostaglandins during Labor

Effects of the Prostaglandins on the Uterus

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