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)

The inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the "Post-Proline Cleaving Enzyme", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal.
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PMID:Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species. 0

Although only about 8 per cent of pregnancies end prematurely, as much as 75 per cent of perinatal deaths are due to prematurity. Since it is difficult to identify the predisposing factors in individual cases and to prevent the premature onset of labor, it is necessary to try to arrest such labor when it occurs. A theoretical scheme for the mechanism of labor in the human subject is presented. This permits the identification of four possible points of attack: (1) replacement of progesterone to reduce the myometrial sensitivity to oxytocin, (2) administration of beta-mimetic agents to relax the uterus and make it unresponsive to stimuli, (3) administration of ethanol to block oxytocin secretion, and (4) administration of anti-inflammatory drugs to inhibit prostaglandin synthesis. Results obtained with ritodrine, a beta-mimetic agent, and with ethanol are presented as illustration. Ritodrine gave somewhat better results than ethanol, possibly because the treatment was continued after discharge of the patients.
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PMID:Prevention of prematurity. 1 89

Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine.
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PMID:Effect of ritodrine on uterine activity, heart rate, and blood pressure in the pregnant sheep: combined use of alpha or beta blockade. 1 90

Effects of methyl O-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400), a new antihypertensive agent, on the peripheral nervous system in mice, rats and guinea pigs were investigated and compared with effects of reserpine and rescinnamine. Oral administration of CD-3400 in doses from 40 to 320 mg/kg revealed a miotic action and such was weaker than that seen with reserpine and rescinnamine. The intestinal propulsion in mice was accelerated by pretreatment with reserpine, but no so with CD-3400. In isolated guinea pig vas deferens, CD-3400 at a concentration of 1 X 10(-5) M inhibited on norepinephrine-induced contraction non-competitively. However, in insolated rat vas deferens pretreated with CD-3400 (1 mg/kg, i.p.) for 5 days, norepinephrine-induced contraction was potentiated and this effect was weaker than that seen with reserpine and rescinnamine. In isolated rat vas deferens pretreated with CD-3400 for 1, 2 and 5 days,, the contraction induced by tyramine (3 X 10(-5)M) was significantly inhibited. The effect was qualitively similar to those of reserpine and rescinnamine. The intravenous administration of these three rauwolfia alkaloids in doses of 1, 2 and 4 mg/kg had no effect on the spontaneous movement of rat uterus. In isolated rat uterus pretreated with CD-3400, no significant effect was observed on oxytocin- and isoproterenol-induced responses. The peripheral actions of CD-3400 are attributed to a deterioration in the function the sympathetic nerve resulting in depletion of catecholamine stores. Efect of CD-3400 were slightly weaker than those of reserpine and rescinnamine.
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PMID:[Effects of methyl O-(4-hydroxy-3-methoxycinnamoly)reserpate (CD-3400) on the peripheral nervous system: especially on the smooth muscle organs]. 1 72

Isamide, the N-chloroacetyl derivative of 5-methoxytryptamine, produced a dose-dependent competitive blockade of uterine contractions in vitro induced by 5-HT. The pA2 value for the 5-HT-isamide interaction was 4.42. The blockade was short-lasting and reversible; after recovery, a dose-dependent increase in the uterine sensitivity to 5-HT was found. The blockade proved to be selective to the 5-HT receptor. The simultaneous application of 5-HT plus isamide partially prevented the 5-HT-induced auto blockade phenomenon. In addition, isamide did not affect the contractile responses of the uterus to oxytocin or bradykinin or the contractile effects of the rat vas deferens to adrenaline.
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PMID:N-Chloroacetyl 5-methoxytryptamine (isamide): a selective antagonist of 5-hydroxytryptamine in the rat uterus. 3 34

The various neurohumoral and intrinsic factors that control the uteroplacental hemodynamics in health and disease and in responses to physiologic and pharmacologic stimuli have been reviewed. The following conclusions may be derived: We still need improvement in our methodology of monitoring uterine blood flow. The present methods, which have some reliability, are not easily applicable to human subjects and even in animals their use presents problems of accuracy and sensitivity with which the investigator must become familiar. The marked and progressive increase in uterine blood flow that occurs during pregnancy is caused by complex factors, some of which are hormonal and hemodynamic in nature. The increased vascularity of the pregnant uterus and the opening of the arterioles during the process of formation of the intervillous space are important factors that facilitate the increase in uterine blood flow. The increment seems to be totally derived from the increment in the cardiac output that occurs during pregnancy. There seems to be no redistribution among the regional blood flows of the body. In the anesthetized condition the blood flow to the uterus depends largely on the perfusing pressure; the critical closing pressure seems to be around the 40 mm Hg level. This linear flow-pressure relationship does not, however, apply to the unanesthetized condition. A rise or fall in the perfusing pressure in the conscious state may be accompanied by an increase or decrease in the uterine blood flow, depending on the underlying mechanisms. Factors that lead to alpha-adrenergic stimulation produce an increase in uterine vascular resistance and a decrease in flow, irrespective of the status of the perfusing pressure. beta-adrenergic stimulation may increase uterine blood flow either through their vasodilating action or through their myometrial relaxing effects. Hypertensive diseases are most often accompanied by a decrease in uterine blood flow, whereas hypoxic states may decrease the flow even though the arterial pressure may not change significantly. It is extremely risky to extrapolate from information obtained in the anesthetized animal to the unanesthetized, conscious animal. Likewise, data obtained from normotensive conditions may not hold true for the hypertensive or hypotensive states. This is of particular relevance when one is dealing with the effects of pharmacologic agents that act on the cardiovascular system. Uterine contractions, whether induced through spontaneous or oxytocin-induced labor, produce a decrease in uterine blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of the uteroplacental circulation in health and disease. 4

Prostaglandins are highly potent derivatives of unsaturated fatty acids with multiple biological activities. They are synthesized and metabolized in almost all tissues studied so far. The E- und F-type prostaglandins may be regarded as local modulators of hormonal effects on cell function and--in some cases (kidney, uterus-corpus luteum)--as regional or tissue hormones. Thus they seem to be involved in the regulation of neurotransmission, kidney function, triglyceride metabolism in adipose tissue and progesterone biosynthesis. Apart from their influence on renal blood flow prostaglandins of the A-type possibly have an additional function as circulatory hormones regulating blood pressure. Second messenger-systems (cAMP, Ca++-cGMP) which mediate the effects of most non-steroidal hormones are also involved in the action of prostaglandins, at least of the E-and F-types. Disturbances in prostaglandin metabolism (increased or decreased biosynthesis) are discussed to play a role in the pathogenesis of inflammation, pain, fever, hypertension, bronchial asthma and gastric or duodenal ulcer formation. Drugs with antiinflammatory, analgesic and antipyretic activity have been shown to be potent inhibitors of prostaglandin formation. The correlation of a local prostaglandin deficit or the therapeutic use of single effects of prostaglandins by administration of exogenous compounds (natural prostaglandins or modified derivatives) has so long been less satisfactory because of their large number of biological actions which lead to undesired side effects. Extensive experience have been obtained in the successful induction of therapeutic abortion. This effect is based on the stimulatory action of E- and F-type prostaglandins on the smooth muscles of the pregnant uterus which is resistent to the influence of other stimuli, e. g. oxytocin. Here the incidence of side effects could be reduced by local administration of low doses of prostaglandins into the uterine cavity. A general improvement of the therapeutic usefulness of prostaglandins will however only be achieved, if modified derivatives with more specific actions on the desired "target" tissues are available.
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PMID:[Biology of prostaglandins with reference to therapeutic aspects]. 16

This investigation was undertaken to evaluate the functional contribution of the peptide backbone of oxytocin in its interaction with receptor. Corey-Pauling-Koltun models of (Gly-7) deaminooxytocin, deaminotocinamide, and their respective retro-D-analogs built in any specific conformation (e.g., the Walter-Urry model for oxytocin) have a quai-equivalent topochemical arrangement of amino-acid side chains; however, the CO and NH elements of the peptide backbone of the retro-D-analog are reversed. The retro-D-analogs of deaminotocinamide and (Gly-7) deaminooxytocin (prepared using D-alle for L-Ile) and their respective N-formyl derivatives were assayed for uterotonic activity relative to related L-peptides. All retro-D-analogs (tested at concentrations ranging from 10-10 to 10-5 M) were devoid of angonistic (or antagonistic) activity in the isolated rat uterus, except for the retro-D-(D-alle-3, Gly-7) deaminooxytocinamine, which retains a terminal NH-2 group on the tail; the latter is a partial agonist with very low affinity. The results obtained with retro-D-analogs indicate that one or more of the elements of the peptide backbone of the tocinamide ring are essential for "occupation" and "activation" of uterine receptors. Oxytocin action may be the resultant of multiple hydrogen-bonding interactions between CO, NH, NH-2, and OH groups of the hormone with complementary groups on receptor, made possible by appropriate hydrophobic bonding.
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PMID:Contribution of the peptide backbone to the action of oxytocin analogs. 16 58

CAMP levels of isolated rat uteri (2nmol/g wwt) were increased by Fenoterol (10(-4)--1 mug/ml) in a dose dependent manner reaching concentrations of more than 10nmol/g withing 2--5 min. AT 2 TIMES 10(-3) MUG/ML Fenoterol inhibited spontaneous contractions of the rat uterus in vitro. A 10,000 fold higher dosis of Fenoterol was needed to elicit a similar degree of inhibition, when contractions were induced by 0.6 mU/ml Oxytocin. However cAMP levels were elevated by Fenoterol in presence of Oxytocin, uterine contractions were not inhibited, i.e. the elevation of cAMP after administration of Fenoterol is correlated with a relaxant effect only in uteri contracting spontaneously.
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PMID:[Influence of fenoterol of cAMP levels and motility on the rat uterus in vitro (author's transl)]. 16 93

Recordings of intratubal pressure in women reveal a complex pattern of tubal contractions. Overall activity of the fallopian tube is increased during ovulation. During the luteal phase of the menstrual cycle, activity is depressed but never suppressed. The fallopian tube remains active during gestation in contrast with the uterus which is quiescent. The early puerperal tube displays a pattern of activity similar to that recorded during the late luteal phase of the menstrual cycle. Activation occurs during suckling and in response to exogenous oxytocin, prostaglandins, nor-adrenergic compounds, and ergot derivatives. It is concluded that contractility of the fallopian tube is less influenced by ovarian steroids than that of the uterus.
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PMID:Contractility of the fallopian tube. 17 Jan 70


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