• The Korean Journal of Physiology and Pharmacology
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• 제26권4호
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• pp.255-262
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• 2022

Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10^-9-10^-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10^-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.

• 한국가축번식학회지
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• 제22권1호
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• pp.61-66
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• 1998

In vitro contractile response of the uterus in the pregnant rat to oxytocin increases with advancing gestation. This increase coincides with an increase in uterine oxytocin receptor number. However, in vitro the change in uterine contractile response of the pregnant uterus to oxytocin with advancing gestation is not clear. The purpose of the present study was to find out that the uterine response in vitro to oxytocin changes as delivery a, pp.oaches. Secondly, to determine if the incubation of uterine tissue in vitro altered the uterine oxytocin receptor number and affinity and thus explain the ambiguity between the in vitro and in vitro results. The studies were performed on rats at days 15, 20 and 21 or pregnancy. In vitro the uterine contractile response to oxytocin was sgreater (P<0.05) at day 21 compared to days 15 and 20 (Emax : 724.8　88.9, 130.0　81.5 and 133.4　53.4, respectively). This correlated with a significant increase (P<0.05) in uterine oxytocin receptor number at day 21 (days 21, 15 and 20 : 540　89, 53　24, 89　35 fmoles/mg protein, respectively). However, the kids at days 15, 20 and 21 did not differ (P>0.05). Finally no difference (P>0.05) in oxytocin receptor number or affinity was detected between incubated and non-incubated tissue. The results of these studies suggest that either pre-oxytocin or post-oxytocin receptor factors are important in determining the uterine myometrial responsiveness to oxytocin.

• Journal of Pharmaceutical Investigation
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• 제1권1호
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• pp.34-46
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• 1971

The existence of oxytocin in the pituitary gland of chicken has been ascertained, but its physiological roles are still obscure. In the study the action of oxytocin on renal function of the chicken was investigated during water diuresis, utilizing clearance and the Sperber technique. The results obtained are summarized as follows: Oxytocin, like in many species of mammals, elicited a profound diuretic response in the chicken. Urine flow, excretion of electrolytes, as well as glomerular filteration rate increased, with intravenous infusion of $3{\sim}10\;m{\mu}/kg/min$. Oxtocin, infused into the renal portal circulation via hindleg vein in a dose of $3{\sim}13\;m{\mu}/kg/min$. elicited marked increase in urine flow, glomerular filteration rate and sodium excreted in the urine. The diuretic effect was more pronounced in the infused side. It is suggested that diuretic response to oxytocin in the chicken results from dual action of oxytocin: increase of GFR and inhibition of sodium reabsorption on the renal tubule. The possibility that oxytocin might act through some endogenous substances could be ruled out.

• 한국가축번식학회지
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• 제18권2호
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• pp.95-99
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• 1994

우수성이 이미 입증된 oxytocin antagonist-I(AI)이 발정된 쥐의 자궁내 옥시토신 수용체 수와 결합친화력이 어떤 영향을 미치는 지를 알아보는 것이 본 연구의 목적이었다. 마취된 흰쥐들에게 5$\mu\textrm{g}$의 AI를 투여하였으며, 30분과 4시간후에 도살하였다. 자궁조직을 회수하여 잘게 잘라 냉동시킨 다음 다시 자궁조직을 분쇄한 후 단계적인 초고속 원심분리를 거쳐 옥시토신 수용체가 있는 세포막을 추출하였다. 옥시토신 수용체 분석은 높은 활동성을 보이는 옥시토신 길항제와 방사선 동위원소가 붙지 않은 옥시토신이 경쟁하는 포화상태에서 실시하였다. 옥시토신 수용체의 수와 결합친화력은 nonlinear curve fitting 방법에 의해 계산되었다. 연구 결과, AI이 투여된 흰쥐들은 수용체의 수와 결합력에 있어서 control과 유의한 차이를 보이지 않았다(p>0.05). 결론적으로 AI은 옥시토신 수용체의 수와 결합친화력을 변화시키지 않고 다만 옥시토신과 경쟁력으로 억제하는 작용을 옥시토신 수용체에서 나타낸다는 것을 이 연구에서 입증하였다.

• 대한약리학회지
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• 제23권2호
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• pp.133-141
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• 1987

Acetylcholine및 oxytocin에 의하여 야기되는 흰쥐의 적출자궁수축을 $Ca^{2+}$ 길항제의 일종인 verapamil및 tetracaine 존재하에서 acetylcholine및 oxytocin에 의한 자궁수축곡선을 4개의 요소 (trough tension, T: peak tension, P; contraction frequency, F: duration, D)로 나누어 비교분석하여 다음과 같은 결과를 얻었다. Verapamil $(0.25\;{\mu}M)$은 자발수축을 억제시켰으나 tetracaine$(42\;{\mu}M)$은 자발수축을 억제시키지 못하였다. 이들 길항제의 존재하에서 acetylcholine및 oxytocin에 의하여 야기되는 자궁수축의 각 구성요소에 변화를 관찰하였다. 즉 acetylcholine에 의한 수축에서 verapamil은 P와 D를 감소시켰고 tetracaine은 F를 감소시키고 D를 증가시켰다. oxytocin에 의한 수축에서 verapamil은 P와 D를 감소시켰으나 tetracaine은 oxytocin농도에 따라 차이가 있었는데, 저농도의 oxytocin에 의한 수축에서는 F를 감소시키고 D를 증가시켰으나 고농도의 oxytocin에 의한 수축에서 는 F와 D에는 영향을 주지 않고 P만 감소시켰다. 이상의 결과로 미루어 acetylcholine및 oxytocin에 의하여 야기되는 수축곡선은 시각적으로 큰 차이가 없었으나 작용기전이 다른 $Ca^{2+}$ 길항제에 의하여 acetylcholine및 oxytocin의 수축의 구성요소에 다르게 영향을 미칠 수 있었다는 것은 수축곡선의 구성요소의 변화를 면밀히 검토하면 자궁수축제의 수축작용기전이 다름을 예측할 수 있을 뿐만 아니라 수축억제제에 의한 억제 기전의 차이점도 예측할 수 있을 것으로 생각되어 진다.

• 한국가축번식학회지
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• 제18권2호
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• pp.101-104
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• 1994

임신기간중 oxytocin의 역할을 규명하기 위해 그리고 조기분만 진통의 억제제로서 수많은 강력한 oxytocin antagonist들이 개발되고 있다. 본 연구는 발정된 흰쥐를 사용하여 oxytocin antagonist I(AI)이 control과 비교하여 자궁에 어떠한 활동을 보이는지를 알아보는 것이 주 목적이었다. AI과 control로서 saline을 주입하기 위해 경정맥에 cannula를 수술하여 집어 넣었고, 또 다른 cannula는 자궁활동을 측정하기 위해 자궁각에 집어 넣었다. 자궁수축상호아은 Grass Polygraph를 사용하여 측정하였고 수축활동은 10분동안의 integrated area를 계산하여 측정되었다. 5$\mu\textrm{g}$의 AI을 주입한 5분후 100mU의 oxytocin이 주입되었고 이 oxytocin주입은 매시간 5시간 동안 계속되었다. AI이 주입된 5분 후, oxytocin에 대한 자궁의 수축반응은 control에 비해 77% 감소되었다(P<0.05). AI 주입 2시간 후에는 그 감소가 control에 비해 54%였다. 그러나 3시간 이후부터 AI은 control과 어떤 유의한 차이를 보이지 않았다. AI이 인간의 조기분만진통을 방지하는데 사용될 수 있다는 잠재 가능성을 본 연구에서 확인하였다.

• Journal of Korean Biological Nursing Science
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• 제24권1호
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• pp.1-16
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• 2022

Purpose: Recently, oxytocin has been introduced experimentally as a pharmacological treatment for post-traumatic stress disorder (PTSD). This study attempted to investigate the possibility of oxytocin as a treatment option for patients with PTSD by examining its dose, interval, and effectiveness in patients with PTSD. Methods: A systematic review was done on articles published from 1967 to 2020 using the PubMed, PsycINFO, and Cochrane databases. Our inclusion criteria were 1) subjects 18 years of age or older diagnosed with PTSD or exposed to a traumatic event that met criterion A of the Diagnostic and Statistical Manual of Mental Disorders (DSM) for PTSD, 2) oxytocin was administered at least once, 3) clinical trials, and 4) studies published in Korean or English. Two independent researchers reviewed 22 articles and recorded the contents. The risk of bias was evaluated to determine the quality of the reviewed article. Results: The parameters for evaluating the effectiveness of oxytocin were identified as socio-behavioral measures in 11 articles, neuronal imaging in 9, and biomarkers in 4. In 5 papers, oxytocin was administered multiple times. Socio-behavioral measures were improved in 3 out of 5 studies in which oxytocin was administered multiple times. In 2 studies in which prolonged exposure treatment and nasal oxytocin administration were combined for 10 weeks, patient symptoms were decreased compared to the control group. Conclusion: The possibility of oxytocin as an adjuvant treatment for PTSD psychotherapy was confirmed. Further studies are necessary to evaluate the long term effectiveness of administering oxytocin multiple times combined with psychotherapy.

• Asian-Australasian Journal of Animal Sciences
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• 제14권11호
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• pp.1523-1526
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• 2001

To study the secretion of trace elements during early lactation, twelve lactating Murrah buffaloes were selected from the herd of the institute. The buffaloes were divided into two groups of six each. Buffaloes of group I were not injected and served as control. Buffaloes of group II received oxytocin injection (2.5 I.U.) intramuscularly for a period of five days for let down of milk. Milk samples were collected from both groups of buffaloes five days before, during and after the administration of oxytocin. Aliquots of milk samples from each buffalo were composited in proportion to their milk yield and used for analysis of trace elements in milk. In both the groups of buffaloes Cu, Mg, Fe, Zn and Mn contents did not vary significantly between animals. However, Ca levels varied significantly (p<0.01) between animals. Administration of oxytocin influenced (p<0.01) Cu, Mg, Zn, Fe and Mn secretion in milk. However, Ca secretion was not affected by oxytocin administration. Secretion of these elements also varied significantly during different days of the study. Zinc content of milk in the control group also varied significantly (p<0.01) during different days and periods of study indicating thereby no effect of oxytocin. The study indicated that administration of oxytocin increases Cu and Mn content and decreases Mg, Fe and Zn content without altering the Ca concentration of milk.

• Journal of Yeungnam Medical Science
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• 제9권2호
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• pp.359-381
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• 1992

Benzodiazepine계 약물들은 진정 최면제의 대표적인 약물로서, 중추신경계에서의 그 작용은 gamma amino butyric acid(GABA) 수용체와 짝지워져 있는 benzodiazepine 수용체를 통해서 나타나며 또한 뇌에 있는 synaptosome에서 전위 의존성 calcium channel을 통한 calcium의 섭취를 억제함으로써 진정작용 및 최면 작용이 나타난다. 이와 아울러 말초 장기에서도 benzodiazepine 수용체와 GABA 수용체가 발견 되었는데 이들의 기능과 상호관계는 잘 알려져 있지 않다. 이에 본 실험에서는 benzodiazepine계통의 대표적인 약물이며 중추신경과 말초 장기에 동시에 작용하는 diazepam이 흰쥐 적출자궁의 자발 수축 및 oxytocin 유발 수축에 미치는 영향을 검색하고, 이러한 diazepam의 효과와 GABA 수용체 및 calcium과의 상호관계를 검색함으로써 그 작용기전을 추구해 보기 위하여 다음과 같은 실험을 하였다. 난소를 제거한 후 estrogen(17 beta-estradiol : $500{\mu}g/kg/day$)을 4일 동안 전 처치한 흰쥐의 자궁을 적출하여 등척성 장력을 측정함으로써 그 수축력의 변화를 관찰하였다. Diazepam과 GABA 수용체 효현제 및 그 봉쇄제들이 자궁절편의 자발 수축과 oxytocin 유발 수축에 미치는 영향을 검색하였고, 또 이들 약물의 작용에 관련된 calcium 동원기전에 대하여 관찰하여 다음과 같은 결과를 얻었다. Diazepam은 흰쥐 적출자궁의 자발수축 및 oxytocin 유발수축을 농도 의존적으로 억제하였다. GABA, GABA A 수용체 효현제인 muscimol, GAGA A 수용체의 상경적 봉쇄제인 bicuculline, GABA A 수용체의 비상경적 봉쇄제인 picrotoxin, GABA B 수용체 효현제인 boclofen, 그리고 GABA B 수용체 봉쇄제인 delta-aminovaleric acid는 흰쥐 적출 자궁의 자발 수축 및 oxytocin 유발수축에 아무런 영향을 미치지 않았다. 자발 수축 및 oxytocin 유발수축에 대한 diazepam의 억제 작용은 GABA 수용체 효현제 및 봉쇄제의 영향을 받지 않았다. 그러나 bicuculline은 diazepam의 억제 작용에 상가적으로 작용하였는데, bicuculline의 이러한 작용은 muscimol에 의해서 길항되지 않았다. 정상 PSS 내에서 diazepam에 의해 억제되었던 자발수욱 및 oxytocin유발수촉은 calcium의 첨가 및 calcium inophore인 A23187의 첨가로 일부 회복되었다. Calcium 배제 용액내에서는 diazepam이 calcium 첨가로 인한 수축력 회복을 방해하였으며 calcium inophore인 A23187에 의한 수축력 증가는 막지 못하였다. 또 세포외액에 calcium이 결핍된 상태에서는 oxytocin 자체에 의한 수축을 방해하지 못하였으나 이어 첨가된 calcium에 의한 oxytocin 유발 수축의 증가는 일부 억제하였다. 이상의 실험결과로 미루어 볼 때 diazepam은 자궁의 자발수측 및 oxytocin 유발 수축을 억제할 수 있으며, 이러한 작용은 GABA 수용체 의존성이 아닌 세포외액의 calcium의 유입을 억제함으로써 나타나는 것으로 사료된다.

• Reproductive and Developmental Biology
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• 제30권4호
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• pp.307-311
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• 2006

The purpose of this study was to determine effects of oxytocin and $interleukin-1{\alpha}$ on in vitro development of bovine embryo cultured with endometrial epithelial and stromal cells isolated from bovine uterus. The expressions of COX-2 mRNA in bovine endometrium were also studied. When embryos were cultured with epithelial cells, the rate of blastocysts was significantly (p<0.05) higher in embryos treated with oxytocin than that of control group. The rate of hatched blastocysts was also significantly (p<0.05) higher in embryos treated with oxytocin than those of two control groups. On the other hand, when the embryos were cultured with stromal cells, the rate of blastocysts were significantly (p<0.05) higher than those of groups treated with $IL-1{\alpha}$, oxytocin and control with stromal cells than that of control group without stromal cells. The rate of blastocysts hatched were also significantly (p<0.05) higher in group treated with $IL-1{\alpha}$ than those of control group without stromal cells and oxytocin group. In another experiment, COX-2 gene was expressed in embryo group treated with oxytocin during the co-culture of embryos with epithelial cells. In contrast, COX-2 mRNA was expressed in group treated with $IL-1{\alpha}$ when the embryos were cultured with stromal cell. This result shows that oxytocin and $IL-1{\alpha}$ were stimulate embryo development in vitro when embryos were cultured with epithelial and stromal cells, and can affect the development of bovine embryos in the uterus.