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)

1. Two enzymes acting on the linear portion of oxytocin: carboxamidopeptidase (releasing Gly . NH2) and prolyl peptidase (releasing Leu-Gly . NH2) were identified in the cytoplasmic fraction of chicken liver. 2. Carboxamidopeptidase was purified 134-fold with a 23% yield, and prolyl peptiase 71-fold with a 20% yield. The specific activity of the final preparations was 181 and 96 microU/mg protein, respectively. 3. The optimum pH for carboxamidopeptidase was 6.0--6.5 and for prolyl peptidase, 7.5. Carboxamidopeptidase activity was inhibited by Mn2+, Zn2+, Ca2+, Co2+, and stimulated by EDTA; the activity of prolyl peptidase was inhibited by Zn2+ and Mn2+. The Km value of both enzymes for oxytocin was 1.5--2.4 microM.
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PMID:Partial purification and characterization of the oxytocin-inactivating enzymes from chicken liver. 39 2

The influence of oxytocin on the electrical and mechanical activity of uterine smooth muscle strips was studied under voltage-clamp conditions. 1. At a concentration of 0.1 mU/ml, oxytocin caused a slight depolarization of the resting potential and also increased the amplitude of the action potential. The maximal frequency of the rhythmic activity, which can be produced by depolarizing current pulse, is increased by about 20%. 2. Oxytocin increased the peak of the inward current without modification of the reversal potential. This effect is enhanced in a sodium-free solution. With oxytocin the steady-state inactivation of the inward current is not modified and the increase in the current intensity can be related to an increase in the maximal conductance. The amplitude of the outward current is not affected. 3. The first component (phasic-like) of the contractile response obtained for brief depolarizations is increased by oxytocin. This effect may be explained by the increase in the intensity of the inward current. The second component (tonic-like) of the contraction associated with long-lasting depolarizations and obtained in manganese-containing solution is not modified. The increased frequency of the rhythmic activity after oxytocin administration may also result in increased contractility by summation.
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PMID:Effects of oxytocin on ionic currents underlying rhythmic activity and contraction in uterine smooth muscle. 94 44

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
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PMID:Aminopeptidase P from human leukocytes. 144 89

To identify and characterize oxytocin receptors, a 125I-labeled photoreactive oxytocin antagonist was synthesized. The specific oxytocin antagonist [1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid), 2-O-methyltyrosine,4-threonine,8- ornithine,9-tyrosylamide]oxytocin ([Mca,Tyr(O-Me)2,Thr4,Orn8,Tyr9-NH2]oxytocin) described by Elands et al. (Elands, J., Barberis, C., Jard, S., Tribollet, E., Dreifuss, J.-J., Bankowski, K., Manning, M., and Sawyer, W. H. (1987) Eur. J. Pharmacol. 147, 192-207) bound to the guinea pig uterine oxytocin receptor with high affinity (apparent Kd = 0.74 nM). The introduction of a 4-azidophenylamidino group at Orn8 resulted in the photoreactive ligand [Mca1,Tyr(O-Me)2,Thr4,Orn(4-azidophenylamidino)8,Tyr9- NH2]oxytocin, which retained the high binding affinity (Kd = 0.69 nM) of the parent compound. The photoreactive antagonist monoiodinated at Tyr9 had approximately double (Kd = 0.39 nM) the affinity of the photoreactive antagonist and several times that of oxytocin (Kd = 2.6 nM) for the guinea pig uterine oxytocin receptor. In photo-affinity labeling experiments using myometrial membranes obtained from guinea pigs during late pregnancy, the 125I-labeled photoreactive antagonist specifically labeled a protein with an apparent molecular mass of between 68 and 80 kDa: the labeling of this protein was completely suppressed by a 100-fold molar excess of oxytocin and oxytocin receptor-specific agonists, but not by vasopressin analogues specific for V1 or V2 receptors or by other peptide hormones. The ability of oxytocin to suppress labeling was decreased in the presence of guanosine 5'-O-(thiotriphosphate) or in the absence of Mn2+. Digestion of the photolabeled oxytocin receptor with endoglycosidase F gave rise to a protein with an apparent molecular mass of 38 +/- 2 kDa. The endoglycosidase F effect and the lack of endoglycosidase H action show that the myometrial oxytocin receptor is highly glycosylated with asparagine-linked complex oligosaccharide chains. Our results suggest that the radioiodinated photoreactive oxytocin antagonist could be a helpful tool in the isolation and further characterization of the oxytocin receptor.
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PMID:Identification and enzymatic deglycosylation of the myometrial oxytocin receptor using a radioiodinated photoreactive antagonist. 165 65

1. Intracellular current and voltage clamp recordings were obtained from rat supraoptic nucleus neurones in superfused hypothalamic explants in order to evaluate their response to dopamine and to D1 and D2 agonists. 2. With one exception, exposure to dopamine (10-200 microM) depolarized supraoptic neurones. When tested for an effect on twenty-one spontaneously active supraoptic neurones, dopamine enhanced the firing of all eleven continuous-firing (possibly oxytocin-secreting) neurones and prolonged the burst in all ten phasic-firing (vasopressin-secreting) neurones. 3. In sixty-seven of sixty-eight neurones where current injection was used to maintain membrane potential below threshold for action potential generation, current clamp data revealed that exposure to dopamine (10-200 microM) was followed in 10-17 s by a gradual 3-7 mV membrane depolarization that lasted for 4-15 min and was accompanied by a 12-23% reduction in input resistance. Exposure to quinpirole, a D2 agonist (10-200 microM), induced a similar response with comparable onset, duration and change in input resistance. In contrast, tests on sixteen cells indicated little or no response to a D1 agonist SKF38393. 4. Under voltage clamp, dopamine was noted to induce an inward current, accompanied by a 7.5-40% increase in membrane conductance over the corresponding time course. 5. Voltage-current plots for dopamine-induced depolarizations were linear in the range -50 to -110 mV. Dopamine and quinpirole depolarizations had extrapolated mean reversal potentials of -25 +/- 10 mV (mean +/- S.D.) and -20 +/- 15 mV respectively. This approximated the mean reversal potential of -20 +/- 8 mV measured from the dopamine-induced inward current using single-electrode voltage clamp. 6. The actions of dopamine were selectively antagonized by two D2 receptor antagonists, sulpiride and spiperone, but neither influenced membrane depolarizations induced by equimolar concentrations of noradrenaline. Dopamine-induced depolarizations also persisted following selective blockade of alpha 1-adrenergic receptors by prazosin; under these conditions, noradrenaline induced membrane hyperpolarization. 7. Following complete substitution of external Na+ with Tris, the reversal potential for the dopamine-induced response was shifted to -70 +/- 9.8 mV. This value was consistently less negative than the estimated potassium equilibrium potential. 8. The depolarization action of dopamine persisted in media containing tetrodotoxin and with an external calcium concentration ([Ca2+]o) of 0 mM-Ca2+ with 6 mM-Mg2+ or Mn2+, but was abolished following intracellular injection of [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a Ca2+ chelator.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine D2 receptor activation depolarizes rat supraoptic neurones in hypothalamic explants. 168 25

The demonstration that endothelin (ET) induces rat uterine contraction, coupled with the observation that ET is present in human amniotic fluid, suggests that the myometrium may be an important target organ for this hormone. We show that in quiescent human myometrial cells ET produced a dose-dependent increase in cytosolic free Ca2+ (Cai2+), which was markedly attenuated when the cells were studied in Ca2(+)-free media. Preincubation with nicardipine, diltiazem, or verapamil reduced the ET-evoked Cai2+ transient by 30, 40, and 65%, respectively. The presence of voltage sensitive Ca2+ channels was demonstrated by Mn2+ quenching of fura-2. Activation of the Na+/H+ antiport could not be demonstrated with ET stimulation. In nonquiescent cells, the ET-evoked Cai2+ transient was significantly reduced, while the response to oxytocin was retained. This is at least partially explained by a reduction in Bmax (maximal binding capacity) for ET (mean +/- SEM) from 3,506 +/- 268 binding sites/cell in quiescent cells to 2,411 +/- 300 binding sites/cell, as well as 72% increase in Kd (equilibrium dissociation constant), in the nonquiescent cells. We conclude that, in human myometrial cells, ET and oxytocin modulate Cai2+ through independent receptors and propose that ET, like oxytocin, is an important endogenous modulator of uterine contractility.
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PMID:Endothelin- and oxytocin-induced calcium signaling in cultured human myometrial cells. 184 47

1. Isolated neurosecretory nerve endings were prepared from rat neurohypophyses. The amount of vasopressin (AVP) and oxytocin released was measured by radioimmunoassay. 2. The amount of hormone release under resting conditions was not affected by external calcium (Ca2+o). Secretion decreased by ca. 50% when external sodium (Na+o) was replaced by choline or sucrose. 3. Ouabain did not modify the basal AVP release. 4. The Na+ ionophore monensin increased the release of AVP only in the presence of Na+o. This increase was maintained during prolonged exposure to the ionophore and occurred in the presence of Ca2+o only. 5. In the presence of Ca2+o, the amount of evoked hormone release was dependent on the external K+ concentration. Half-maximal activation was achieved with ca. 40 mM-K+. The K+-induced secretion was potentiated in Na+-free solution. 6. Prolonged 100 mM-K+-induced depolarization in the presence of Ca2+o gave rise to a large increase in hormone secretion which decreased with time (t1/2 = 2.5 min). The release could be reactivated after permeabilization of the nerve terminals in the presence of micromolar concentrations of Ca2+. 7. A stepwise paradigm in which Ko+ is incrementally increased to 25, 50, 75 and then 100 mM released more AVP than a prolonged exposure to 100 mM-K+. 8. Veratridine increased the amount of AVP released. This effect was considerably reduced in the absence of Nao+ and abolished in the presence of D600. 9. The depolarization-induced AVP release was blocked by different Ca2+-antagonists. Their effectiveness was nitrendipine = nicardipine greater than Cd2+ greater than Gd3+ greater than Co2+ = Mn2+. 10. The dihydropyridine Bay K 8644 potentiated both the basal and the K+-evoked AVP release. Its maximal effect was obtained with 25-50 mM-Ko+. 11. In conclusion, the isolated neurohypophysial terminals which have both Na+ and Ca2+ channels and release AVP and oxytocin upon depolarization might be an excellent system to study further the mechanisms leading to secretion of neurohormones.
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PMID:Hormone release from isolated nerve endings of the rat neurohypophysis. 245 Sep 99

Oxytocin-binding sites in the endometrium and myometrium of the non-pregnant ewe were characterized. [3H]Oxytocin bound to a single site in both tissues with high affinity; dissociation constants were determined to be 1.96 nmol/l in endometrium and 2.12 nmol/l in myometrium. Oxytocin binding was enhanced by divalent cations with a similar order of potency in both tissues: Co2+ greater than Mn2+ greater than Ni2+ greater than Mg2+ greater than Zn2+ greater than Ca2+. The endometrial and myometrial binding sites showed the same specificity for oxytocin analogues and related peptides, having high affinity for oxytocin, [Arg8]-vasopressin, [Lys8]-vasopressin, and the oxytocin-specific agonists [Gly7]-oxytocin and [Thr4,Gly7]-oxytocin. The results suggest that oxytocin receptors present in the endometrium and myometrium of the ewe are similar both to each other and to classical oxytocin receptors.
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PMID:Characterization of endometrial and myometrial oxytocin receptors in the non-pregnant ewe. 255 41

The effect of vasopressin and oxytocin on the dorsal root potentials were studied in isolated spinal cord of 12-16 days old rats. It was shown that both neuropeptides evoked reversible depression of the dorsal root potential induced by stimulation of the neighbouring dorsal root. Application of vasopressin or oxytocin caused the reversible dose-dependent depolarization in the dorsal root. The depolarization was preserved in Ca2+-free manganese-containing solution. Functional significance of presynaptic effects of hypothalamic neuropeptides is discussed.
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PMID:[Effect of vasopressin and oxytocin on the dorsal root potentials of the isolated perfused spinal cord in rat pups]. 285 81

Mg2+ increases the potency of oxytocin (OT) analogs in stimulating uterine contractions. Generally, the enhancing effects of Mg2+ are inversely related to the potency of the peptide. To determine the site of metal ion action, we measured the effects of Mn2+, another potentiating metal ion, on the ability of a series of peptides to inhibit the binding of [3H]OT to receptor sites on both uterine myometrial and mammary gland plasma membranes. The analogs used in this study were derivatives of 7-glycine oxytocin, which is about 10 times more active when the Mg2+ concentration in the uterine smooth muscle bath is increased from 0 to 0.5 mM. We found a generally good correlation between the ability of the analogs to inhibit [3H]OT binding to both receptor systems and their biological potencies. An increase in Mn2+ concentration from 1 to 10 mM enhanced the affinity of uterine membranes for the analogs, in inverse proportion to their potencies. This selective enhancement occurred regardless of the structural modification of peptide. These results suggest that the metal ion effect occurs at the receptor level and is not a property of the peptide per se. In contrast to the uterus, the affinities of mammary gland receptors for two low potency analogs were unaffected by increased Mn2+ concentration. The mechanisms of the metal ion effect are not entirely understood, but it appears that Mn2+ allows the conformation of the myometrial receptor to adapt to less well-fitting ligands. Although the metal ion effects on mammary gland receptors are more difficult to interpret, it is clear that uterine and mammary gland receptors are different with respect to the mechanisms of interaction with peptides.
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PMID:Binding studies with rat myometrial and mammary gland membranes on effects of manganese on relative affinities of receptors for oxytocin analogs. 301 37


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