家兎剔出子宮에 對한 oxytocin의 作用

Abstract

[한글]

[영문]

The first report of an extract of the posterior pituitary gland having an effect on the uterus was described in an article on "The physiological action of ergot" by Dale(1906). Bell (1907) soon utilized the extract in his Practice and reported that

it effectively reduced postpartum uterine hemorrhage. In 1911, Hofbauer introduced its use to stimulate uterine contraction during labor. Kamm et at. (1928) fractionated posterior pituitary extract into two polypeptide portions: one predominantly oxytocic (oxytocin) and the other predominantly vasopressor and antidiuretic in action(pitressin) anti Du Vigneaud (1951) .successfully synthetized these two polypeptides and described their structural formulas.

Although numerous investigators have shown the uterine contracting activity of oxytocin, the exact effects of this substance on the uterus are uncertain and many features are controversial. This uncertainty arises from species differences in response to oxytocin, the variable effects of the sex hormones on the responsiveness of the uterus and unknown factors influencing uterine activity Knaus (1926) found that estrogen increases spontaneous motility and the response of the human uterus to pituitary extract In reviewing the literature extensively, Henry and Brown (1943)concluded that the spontaneous activity of the human uterus and its sensitivity to pituitary extract are great in the luteal phase of the cycle and by the same token that progesterone is not a uterine sedative. However, the consensus among clinicians, contrary to the finding of Henry and Brown, is that progesterone reduces uterine motility and sensitivity to the posterior pituitary extract.

It is generally known that the responsiveness of the uterus to oxytocin varies during pregnancy and gradually increases to become maximal at term and immediately postpartum. The nonpregnant uterus is known to be much less responsive to this drug. However, no experimental data has been reported to indicate that okytocin produces uterine relaxation. While examing the relationship between the uterine motility and myometrial catecholamines it was found that oxytocin significantly inhibited the motility of the isolated uterine segment from progesterone-treated rabbits. This interesting finding led us to reinvestigate the mechanism of the action of oxytocin on the rabbit uterus.

The experiments were conducted on the isolated segment of the rabbit uterus, which was suspended in a muscle chamber containing 100 ml of Locke's solution, maintained at constant temperature of 38℃. A mixture of 95% oxygen and 5% of carbon dioxide was bubbled through the bathing fluid through a sintered glass plate

at the bottom of the chamber. The spontaneous motility was recorded on a smoked drum by means of an isotonic lever. The uterine segment, after being washed several times with Locke's solution during a period of 30 minutes, attaines a constant

contractility and then drugs were added into the bath.

The epinephrine and norepinephrine concentrations of the uteri were determined according to the procedure described by Shore and Olin (1958).

Results and Discussion

1. Oxytocin exerted a marked stimulatory effect on the pregnant uterine segment, whereas no effect or even inhibitory effect on the non-pregnant uterine segment was seen with high concentrations of this drug.

2. High concentrations of oxytocin produced, without exception, a marked inhibitory effect on the isolated uterine segment from oophorectomized rabbits treated with progesterone for 4 days and a similar inhibitory effect was also observed on this uterine segment with norepinephrine.

3. MJ-1999, [4-(2-isopropylamino-1- hydroxyethyl)methanesulfonanilide], which specifically blocks adrenergic beta-receptor, prevented the inhibitory effects of

oxytocin on the uterine segment isolated from oophorectomized rabbits treated with progesterone, just as it did the response to norephinephrine. Bretylium, which prevent the liberation of adrenergic mediator, rendered the uterine segment unresponsive to the inhibitory action of oxytocin but still allowed it to respond

to norepinephrine. These facts appear to indicate that oxytocin exerts inhibitory effects via release of norepinephrine in the uterus. Finally the inhibitory effect of oxytocin was abolished in the uterine segment from oophorectomized progesterone-treated rabbits whose myometrial catecholamines were almost depleted

by pretreatment with reserpine. This observation strongly suggests that the inhibitory action of oxytocin is mediated via release of norepinephrine.

4. Intramuscular injection of estrogen into the oophorectomized rabbits enhances the sensitivity of their uterine segment to oxytocin. Oxytocin as well as norepinephrine always markedly increased the motility of the uterine segment from oophorectomized estrogen- treated rabbits.

5. Dibenamine (an adrenergic alpha-receptor blockade) and bretylium failed to produce any significant influence on the stimulatory responce to oxytocin of the uterine segment isolated from oophorectomized rabbits treated with estrogen. However, in some cases, these drugs appear to inhibit slightly this stimulatory effect of oxytocin. Similar result was also found on the uterine segment from oophorectomized estrogen-treated rabbits whose myometrial catecholamines were markedly depleted by pretreatment with resepine.

This result suggests that oxytocin produces the stimulatory effect on the uterine segment from oophorectomized estrogen-treated rabbits by directly acting on myometrium. However, there exists some possibility to suggest that an adrenrrgic mechanism ma)r be partly involved in this stimulatory effect of oxytocin.

Summary

Oxytocin exerts an inhibitory effect on the uterine segment isolated from oophorectomized progesterone-treated rabbits. The inhibitory effect of oxytocin is mediated via release of norepinephrine in the uterus. On the other hand, this drug produces a marked stimuatory effect on the uterine segment isolated from oophorectomize destrogen-treated rabbits. The stimulatory effect of oxytocin largely resulted from direct action of this drug on myometrium. However, there exists some possibility to suggest that an adrenergic mechanism may be partly

involved in the stimulatory effect of oxytocin,