Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[8-Lysine]oxytocin was synthesized on a solid support and possessed an oxytocic activity of 100 +/- 6 units mumol on the isolated rat uterus. The epsilon-carbamoyl, epsilon-3-carboxypropionyl and epsilon-3-carboxybutryl derivatives were prepared and had uterotonic activities of 400, 55 and 50 units/mumol respectively. [8-Lysine]oxytocin was coupled unambiguously through the epsilon-amino group to the carboxyl groups of carboxymethylated dextrans or epsilon-3-carboxypropionly-gelatin. The macromolecular oxytocins were water-soluble and retained signigicant oxytocic activity. [8-Lysine]oxytocin should prove a useful ligand for affinity chromatography of oxytocin-binding proteins.
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PMID:Biologically active macromolecular forms of oxytocin. [8-Lysine]oxytocin as a suitable ligand. 88 73

2 cases of undiagnosed abdominal pregnancy observed in a 1-year period are reported. Both were complications of 2nd-trimester induced abortion. In case 1, a 25-year old black woman (gravida 5, para 2), multiple attempts at amniocentesis resulted only in bloody fluid. Intramuscular methyl-prostaglandin F2alpha (PGF2alpha) was administered and hypertonic saline was infused, but neither uterine cramping nor rupture of the membranes followed. PGE2 vaginal suppositories produced no change. Laparotomy revealed a large abdominal mass superimposed on the fundus, extending posterior to the uterus in the cul-de-sac. The amniotic sac contained a 15 ounce stillborn fetus. In case 2, a 33-year old black woman (gravida 2, para 1), bloody fluid was again obtained on amniocentesis. Intravaginal PGE2 suppositories and oxytocin were given, but dilation did not proceed despite uterine cramping. Examination revealed a cystic mass to the right of the uterus and fixed to the cul-de-sac. Laparotomy resulted in removal of a 45 gm macerated fetus. There appeared to be a rent in the right tube from which the gestation had been extruded with secondary implantation upon the abdominal viscera. A 3rd abdominal pregnancy observed in that time period resulted in a live birth at 41.5 weeks of gestation. Clinically, the diagnosis of abdominal pregnancy can be made by sounding the uterus. Laparoscopy will differentiate between abdominal and cornual pregnancy. Sonography is an additional diagnostic aid. When 2nd trimester abortion patients are given PGE2 as a vaginal suppository, 97% abort within 36 hours. Side effects such as vomiting, diarrhea, temperature elevation, and facial flush indicate adequate absorption. When these signs are present but expulsion of fetal tissue or membrane rupture do not occur, extrauterine gestation should be considered.
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PMID:Undiagnosed abdominal pregnancy with inadvertent prostaglandin administration. 90 Jan 63

The dose-response behavior on the in vitro rat uterus of analogs of oxytocin with modification at sites in the molecule which have been predicted to contribute to the binding of the peptide to the smooth muscle receptor have been studied. Dose-response curves of [7-(3,4-dehydroproline)]oxytocin, [7-glycine]oxytocin, [7-alanine]oxytocin, deamino-[7-glycine]oxytocin and [4-threonine,7-glycine]oxytocin were determined and compared with that of oxytocin. The authors found that neither the slope of the curves nor the maximal response obtained for any of the analogs differed significantly from the hormone. The uterotonic potencies of the analogs corresponded to the relative positions along the concentration axis of their dose-response curves and to their affinities as determined by their pD2 values. The authors tentatively concluded that differences in uterotonic potencies of these analogs are in fact the result of differences in their affinity for the uterine receptor. The experimental identification of position 7 of neurohypophyseal peptides as a hormone-receptor binding site corroborates such a proposed role for the side chain of this residue based on earlier conformation-activity considerations.
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PMID:Dose-response behavior on the isolated rat uterus of oxytocin analogs with modifications at binding sites. 90 47

Replacement of the aliphatic isoleucine residue in position 3 of oxytocin (the first corner position of the beta-turn in the 20-membered ring of the solution conformation of the hormone) by phenylalanine has been shown to result in analogues with reduced affinity and intrinsic activity when tested by the individual dose-response procedure on the isolated rat uterus. Studies of effects of structural modifications have been extended to include two additional beta-turn corner positions. First, the dose-response behavior of [Leu4]oxytocin and [Phe4]oxytocin, two analogues in which the Glu4 side chain in the second corner position of the beta-turn in the 20-membered ring has been substituted by hydrophobic and bulky groups, was compared with that of oxytocin. Second, the solid-phase synthesis and biological properties of [Phe3,Leu4,Met8]oxytocin and [Phe3,4,Met8]oxytocin are described. The presence of leucine or phenylalanine in position 4 evokes a drastic reduction in both the affinity and intrinsic uterotonic activity of the resulting analogues, with phenylalanine significantly more effective in reducing intrinsic activity than leucine (p less than 0.001).
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PMID:Conformation-activity studies of oxytocin. Effects of structural modifications at corner positions of the beta-turns on the uterotonic activity. 91 5

[1-(L-2-Hydroxy-3-mercaptopropanoic acid), 4-threonine]oxytocin (hydroxy[4-Thr]oxytocin) and [1-(l-2-hydroxy-3-mercaptopropanoic acid)]oxytocin (hydroxy-oxytocin) were synthesized by a combination of solid phase and classical methods of peptide synthesis. Protected octapeptides were synthesized by the solid-phase method and 1 + 8 couplings in solution were then employed to furnish the required key protected intermediates. Hydroxy[4-Thr]oxytocin has oxytocic potency as measured in the rat uterus suspended in a Mg2+-free solution, of about 4200 units/mg, eight times the potency of oxytocin, while its antidiuretic potency is approximately equal to that of oxytocin. It thus exhibits a significantly favorable oxytocic-antidiuretic sleectivity. Hydroxy-oxytocin has an oxytocic potency of approximatels 1300 units/mt, 2.5 times that of oxytocin. Threonine substitution in hydroxy-oxytocin has thus caused a significant enhancement in both oxytocic potency and selectivity. The enhancement in oxytocic potency of these two peptides relative to oxytocin and [4-Thr]oxytocin appears to correlate with their lipophilic characteristics, suggesting a significant role of lipophilicity in the interplay of oxytocin-like peptides with oxytocic receptors.
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PMID:Synthesis and some pharmacological properties of [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine]oxytocin (hydroxy [4-thr]oxytocin), a peptide with strikingly high oxytocic potency and of [1-(L-2-hydroxy-3-mercaptopropanoic acid)]oxytocin (hydroxy-oxytocin). 94 46

Midtrimester abortion was induced in 529 patients by administration of the naturally occurring prostaglandins E2 and F2alpha as well as the 15-methyl analogs, 15-ME-PGE2 and 15-ME-PGF2alpha. Ten patients failed to abort with prostaglandin therapy, even in association with intravenous oxytocin, a failure rate of 1.9%. Two failures were related to uterine malformation; 1 patient had the pregnancy in a blind uterine horn, and the second patient was pregnant in one horn of a uterus didelphys. Five of the 10 patients who failed to abort during prostaglandin administration were subsequently found to have uterine distortion due to myomata uteri. When abortion induced by prostaglandin fails to occur within the expected time for the agent and technic employed, the presence of uterine malformation or abnormality should be considered. Evaluation with ultrasonography is indicated along with a repeat test to confirm the pregnancy. If the sonogram is suggestive of uterin malformation, a hysterosalpinogram should be obtained to determine if there is communication between the cervix and the gestational sac. If no communication is present, an intravenous pyelogram should be performed in view of the 90% correlation of urogenital abnormalities, and an exploratory laparotomy should be performed. When a communication exists between the cervix and the gestational sac, the 24 hours of uterine activity induced by the prostaglandin will have resulted in cervical changes so that the cervix can easily be dilated to either a 14 or 16 Hegar dilator and the conceptus can be removed in parts with minimal bleeding.
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PMID:Management of failed prostaglandin abortions. 94 38

The relationship between "activator-calcium" (A-Ca), progesterone (P), prostaglandin F2alpha (PGF2alpha) and oxytocin (Oxy) has been examined in 100 uterine strips of 34 pregnant and 100 strips of 34 post partum rabbits. At the 25th day of gestation, uterine P was 13.9+/-1.3 ng/g, while within 3-12 hours post partum 3.3+/-0.3 ng/g tissue (P less than 0.001). Uterine strips, mounted isometrically in Krebs' solution, sustained maximum excitability in a steady state when exposed every 30 seconds for 4 seconds to an electric field of 12 V/5 cm (a.c.). The maximally contracting muscles were then rinsed at intervals of 6 minutes with Ca-free Krebs. In Ca-free Krebs, the post partum uterus lost 31% of its Ca and 96% of its excitability in a short 25 minutes, while the pregnant uterus lost 30% of its Ca and 93% of its excitability in 50 minutes (P less than 0.001). Since the extracellular space is approximately 30% in the uterus, this approximately 30% Ca, lost by both muscles, most probably was extracellular Ca and the small A-Ca fraction which is presumably "bound" more strongly at the membrane systems of the P-dominated pregnant, than the non-dominated post partum uterus. The significantly faster and more complete recovery from Ca-deficiency and inexcitability of the pregnant than the post partum uterus (P less than 0.001), at different levels of external Ca, further substantiates this premise. So does the demonstration that exposure to Ca-free Krebs increases 45Ca-efflux 400% in the post partum and only 110% in the pregnant uterus (P less than 0.001). Exposure to 100 ng/ml PGF2alpha in normal Krebs has a similar effect on the 45Ca-efflux of the post partum uterus, while the response of the pregnant uterus is indistinct (P less than 0.001). These highly significant differences between the post partum and the pregnant uteri in their Ca-efflux explain the higher threshold (P less than 0.001) and lower "sensitivity" to PGF2alpha and Oxy (P less than 0.001) of the pregnant than the post partum uterus. The already very highly significant differences between the two muscles, in threshold and sensitivity to these two most potent oxytocics, were increased still further by rendering the uterine strips Ca-deficient. All together, these findings substantiate the early contention (1-7, 18, 19) that uterine function at the cellular level is regulated by opposing actions of the suppressor P and the intrinsic stimulant PG or other oxytocic agents on threshold, excitability and the Ca-activation of the contractile process.
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PMID:The effects of progesterone, prostaglandin F2alpha and oxytocin on the calcium-activation of the uterus. 95 90

Virgin female Wistar rats were ovariectomized and 2 days later were given a single .2 ml dose of steroid im. Medroxyprogesterone acetate, 100 mg/kg of body weight or estradiol valerate 100 mcg were used. Group 1 (controls) received only solvents, Group 2 received progestogen in saline, Group 3 received the estrogen in oil, and Group 4 received both steroids. On selected days after treatment a rat from each group was killed, the uterus removed, and 2 myometrial strips were suspended in isolated organ baths on Statha G10B strain gauges for isometric recording. After 30 minutes, a dose of either 10 mcg/ml of acetylcholine or .25 mcg/ml of oxytocin was added to each bath. Tension was recorded for 10 minutes followed by a 15-minute wash. These doses were supramaximal. Responses began with a brief contraction and then became a series of fast powerful contrations which continued for 30-60 minutes. Each strip was later removed, prepared for sectioning, and length and cross-section were measured. Controls responded similarly to saline and to oil injections. There was a significnt initial increase in the response to both acetylcholine (p less than .05) and oxytocin (p less than .01). From Days 6 to 20 the responses did not change significantly. After Day 20 the response to acetylcholine declined significantly (p less than .01) but the response to oxytocin was unchanged for the 60 days of the test. With estrogen treatment, increase in response to both spasmogens was highly significant (p less than .001) in the first 18 days at which time it reached a plateau and remained the same for 60 days. With the progestogen treatment the mean response to acetylcholine increased significantly for the first 2 days (p less than .01) then maintained a plateau for the next 3 days equal to the control group and subsequently declined slowly (p less than .001). The contractile response to oxytocin remained constant for 60 days. With estrogen plus progestogen treatment there was a significant increase in contractility up to Day 5 (p less than .001). From Days 5 to 9 plateau levels were maintained with acetycholine and at a lower level with oxytocin. After Day 9 there was a significant decline in both spasmogens effect (p less than .001). With controls and all steroid treatments there was a highly significant difference in responses to acetylcholine and to oxytocin, with acetylcholine consistently giving stronger responses (p less than .001) than oxytocin. Results indicated that medroxyprogesterone acetate required the presence of estrogen for its myometrial action. There was also evidence that estrogen actions were modified by progestogen. It is concluded that single doses of estrogen and progestogen had depot actions of adequate intensity and duration for prolonged studies in myometrial contractility and that there was significant interaction between them when given together. Rat myometrium retained a significant response to spasmogens for at least 60 days after ovariectomy without steroid replacement, perhaps from adrenocortical steroid secretion.
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PMID:Sustained effects on synthetic ovarian steroids of rat myometrial contractility. 96 82

PZ-177 was found to have potent analgesic, anti-inflammatory and mild central depressive actions. In the present work, the general pharmacological actions of PZ-177 were tested in order to investigate other significant actions and to determine the side effects. PZ-177 showed no significant pharmacological activities on the respiratory and cardiovascular system, on the renal function, on the autonomic nervous system, on the sugar level and coagulation in blood and on local irritation. Volume and acidity of gastric juice were decreased and turn over was not inhibited in the connective tissure. Thus PZ-177 was considered to have no ulcerogenic action on the gastric mucosa. The compound relaxed the tonus of isolated small intestine, tracheal muscles and uterus and stopped spontaneous movement. Moreover the contraction of those smooth muscles by such spasmogens as acetylcholine, histamine serotonin, BaCl2 and oxytocin was inhibited by PZ-177 and the activity was almost the same with each spasmogen. It was found therefore to have spasmolytic activity and no specific antagonistic action on the chemical mediators. PZ-177 showed also wear relaxant activity on the skeletal muscle. Those actions on the muscles may have a curative effect on inflammation in bronchotracheal and gastrointestinal tracts or on pain with contraction of skeletal muscle. From the above results, it may be considered that PZ-177 is a relatively safe and useful analgesic and anti-inflammatory compound.
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PMID:[General pharmacological actions of l-(m-chlorophenyl)-3-N,N-dimethylcarbamoyl-5-methoxypyrazole (PZ-177)]. 98 49

To perform episiotomy, 89 women after childbirth were anaesthetized with either halothane (50 patients), methoxyflurane (24 patients) or chloroform (15 patients). The activity of the uterus was registered tocodynamographically. To examine the alternate influence of narcotics and uterotonica, 57 patients were pre-medicated with sintocinon and methergin i.m. as a prophylaxis. The second group (32 patients) received no premedication to stimulate labor activity, however in 18 cases towards the end of narcosis oxytocin and methergin were given i.v. In addition to these examinations 5 vaginal deliveries were anaesthetised with halothane only. Concerning our own experimental study it can be observed: 1. The relaxative properties of halothane wich suppresses completly the activity of myometrium during the deep stages of anaesthesia are superior to chloroform and methoxyflurane. 2. More rapid relaxation of the uterus with halothane compared with chloroform and methoxyflurane. 3. After the use of halothane a quicker return of the activity of the uterus compared with chloroform and methoxyflurane. 4. The value of a prophylaxis with uterotonica can be demonstrated by a comparatively reduced slowing-down of labour-activity during anaesthesia. 5. In every one of the cases, an interuption of the labour-suppressing, caused by the anaesthesia, can be obtained by injecting intravenously oxytocin or methergin. 6. During vaginal delivery, compared to the post placentar phase, there is no need for higher concentrations of halothane to be used to suppress labour contractions. The discussion deals with the intensity of reduction of the uterus contraction caused by the above mentioned narcotics, the dangers of the atony of the uterus, and the indications and contra-indications of obstetrical anaesthesia with halothane or methoxyflurane.
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PMID:[The uterotropismus of halothane, chloroform or methoxyflurane in clinical use (author's transl)]. 99 8


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