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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental studies relating to the direct peripheral vascular actions of neurohypophyseal hormones and their synthetic variants are reviewed. In addition, the available data on the comparative pharmacologic actions of these peptides on mammalian vascular smooth muscle are reviewed. Experiments relating to mechanisms by which neurohypophyseal peptides induce contraction of blood vessels are discussed. Neurohypophyseal peptide hormones appear to be able to contract and relax vascular smooth muscle, the exact type of response being dependent on species, vascular bed, and region within a vascular bed. Receptors that subserve both contraction and relaxation may exist on different blood vessels within a species, with a preponderance of receptors that subserve contraction being present in most blood vessels. Concentrations of vasopressin that can be considered physiologic (i.e., 10(-13) to 10(-11) M) are capable of evoking responses on a variety of microscopic as well as large blood vessels. Arginine-vasopressin appears to be, relatively, the most potent contractile substance on rat blood vessels investigated to date; angiotensin is not. Preservative-free oxytocin is a contractile agent on all mammalian arterial and arteriolar vessels so far investigated. A great deal of the controversy surrounding the exact vascular actions elicited by these peptide hormones can be attributed to many factors that were not controlled in older experiments. Moreover, rat pressor assays cannot be utilized to determine structure-activity relationship for neurohypophyseal peptides on vascular smooth muscles. Nuerohypophyseal peptide-induced contractions of vascular smooth muscles can be markedly affected by sex, sex hormones, alcohols, [Ca2+]0, [mg2+]0, oxygen deficit, and glucose-deprivation. Extracellular sodium and potassium ions appear to play relatively little role in vasopressin-induced contractions of rat arterial smooth muscle. The terminal amino group, phenolic hydroxyl, aromatic ring and basicity in positions 1, 2, 3, and 8, respectively, of the neurohypophyseal hormones are important for optimizing hormone-receptor affinity and intrinsic contractile activity on vascular smooth muscle. Basicity in position 8 of these peptide hormones is not an absolute requirement for contractile activation of these smooth muscles. Alterations in molecular structure can result in neurohypophyseal peptides with unique, and selective, microcirculatory effects that may be beneficial in the treatment of low-flow states.
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PMID:Vascular smooth muscle and neurohypophyseal hormones. 32 65

Luliberin, a luteinizing hormone-releasing hormone, was shown to inhibit the respiratory enzymes of rat liver mitochondria and submitochondrial particles prepared from beef heart mitochondria. At the hormone concentration of 8.10(-6) M the NADH-oxidase activity of the submitochondrial particles was inhibited by 50%. The fragments of the hormone and its analogs and pyroglutamic acid, oxytocin and bradikinin possessed practically no inhibiting effects. In the case of submitochondrial particles the inhibition was only observed in the presence of Ca2+ and was significantly decreased after addition of bovine serum albumin and phospholipase inhibitors -- butacaine and dicaine. It is assumed that the effect of luliberin on the respiratory chain is mediated through mitochondrial phospholipase.
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PMID:[Effect of luliberin on the activities of mitochondrial respiratory enzymes]. 38 96

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

A microsomal fraction was prepared from human pregnant uteri at term and at 6 to 19 weeks' gestation, and from nonpregnant uteri by differential centrifugation and purified on a discontinuous sucrose density gradient. This fraction bound calcium in the presence of adenosine triphosphate (ATP). ATP-dependent calcium binding in microsomal preparations was found to increase with advancing pregnancy. Addition of progesterone increased the ATP-dependent calcium binding, while addition of oxytocin decreased the ATP-dependent calcium binding. In combination, oxytocin and progesterone counteracted each other. The progesterone effect was specific for progesterone; three biologically inactive analogues had no effects on calcium binding. The actions of progesterone and of oxytocin on ATP-dependent calcium binding were found to be consistent with their respective in vivo uterine relaxing and contracting actions.
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PMID:Calcium accumulation by human uterine microsomal preparations: Effects of progesterone and oxytocin. 42 14

Synthesis and biological properties of [5-(N4,N4-dimethylasparagine)]oxytocin are reported. In this analogue, the hydrogens of the primary carboxamide moiety in the side chain of the asparagine residue in position 5 of the posterior pituitary hormone oxytocin have been replaced by two methyl groups. The protected nonapeptide intermediate was prepared by a stepwise procedure using solution techniques. The analogue possesses 4.60 +/- 0.03 units/mg (mean +/- SEM) uterotonic activity on the isolated rat uterine horn and 9.14 +/- 0.03 units/mg of avian vasodepressor activity. Moreover, it displays an identical intrinsic activity in the in vitro rat uterotonic assay as oxytocin, when tested in the presence of either 0.5 mM Ca2+ (standard assay conditions) or at reduced levels of Ca2+ (0.3, 0.15, and 0.05 mM). This result is significant in view of the proposed biologically active model of oxytocin, in which the side chain of the 5 position residue was assigned to contain an "active element" responsible for the intrinsic activity of the hormone when bound to the uterine receptor.
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PMID:Active-site studies of neurohypophyseal hormones: synthesis and pharmacological properties of [5-(N4,N4-dimethylasparagine)]oxytocin. 44 89

Myometrial tissue was obtained from non-pregnant women subjected to hysterectomy because of various gynaecological disorders, and from women undergoing caesarean section. Strip preparations were dissected and isometric tension was recorded. Nifedipine (2.9 X 10(-8)--2.9 X 10(-6)M) inhibited spontaneous contractile activity, mainly by reducing the amplitude of contraction in both non-pregnant and pregnant myometrium. The drug also inhibited potassium induced contractions in a concentration dependent manner. This effect seemed to be more pronounced in pregnant than in non-pregnant tissue. In preparations of pregnant human myometrium, normally polarized or potassium depolarized, oxytocin induced a contractile activity that was effectively inhibited by nifedipine. Nifedipine also relaxed contractions induced by vasopressin in isolated non-pregnant myometrium. It is concluded that the relaxant effect of nifedipine on isolated pregnant and non-pregnant human myometrium can be explained by inhibition of calcium influx. The results thus support the view, that calcium influx is an important step in the initiation of contractile activity in human uterine smooth muscle.
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PMID:Relaxant effects of nifedipine on isolated, human myometrium. 49 17

The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium.
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PMID:Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs. 50 84

1. The central ganglia of a number of gastropod molluscs (including the marine snail Aplysia californica and the terrestrial snail Helix pomatia) contain neurones which exhibit endogenous patterns of oscillatory activity. 2. This oscillatory activity can be modulated for long periods of time by synaptic and hormonal stimulation. 3. Stimulation of appropriate pre-synaptic nerves causes long-lasting hyperpolarization in these neurones, with complete abolition of oscillatory activity. This synaptic response is mediated by an increase in K+ conductance, together with a decrease in inward (Na+/Ca2+) conductance. The ionic conductances affected by synaptic stimulation are those responsible for producing the rhythmic oscillations. 4. The oscillatory activity can also be modulated by the vertebrate neurohyophyseal peptides, vasopressin and oxytocin, and by an endogenous peptide-containing extract of molluscan ganglia. In contrast to synaptic stimulation, these agents cause an increase in oscillatory activity. 5. The endogenous molluscan factor which produces an increase in oscillatory activity can be purified by affinity chromatography on bovine neurophysin linked to Sepharose. This indicates that the molluscan nervous system may contain a neurohypophyseal-like peptide. 6. Oscillatory activity can be modulated by manipulation of cyclic nucleotide metabolism in these neurones. Increases in cAMP alone are associated with abolition of oscillatory activity; this mimics long-lasting synaptic hyperpolarization. Increases in cAMP and cGMP together are associated with an increase in oscillatory activity and mimic the effects of the vertebrate and molluscan peptides. Thus, it is possible that cyclic nucleotides play a role in these physiological responses.
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PMID:Synaptic and hormonal modulation of a neuronal oscillator: a search for molecular mechanisms. 51 75

The author studied the uterine reactivity of alloxan-diabetic rats to oxytocin. Using the Magnus method with Ringer-Locke nutrient solution (modified by Garcia de Jalon) low in calcium and varying the bath temperature from 30 degrees C to 36 degrees C, modifications of the organ were observed. The dose-effect relationship was only practicable in uterus of normal rats at 30 degrees C. When the bath temperature reached 35 degrees C, it was only possible to evaluate the uterine reactivity of alloxan rats by fixed periods of rhythmical contractions, that were graphically represented. This modification in the experiment resulted from the absence of reactivity of the alloxanic rat organ at 30 degrees C. Besides describing the methodology applied, the author suggests a hypothesis about the role of Ca++ on the variation of uterine reactivity. A previous administration of diethylstilbestrol (estrogenic hormone) in alloxanic rats, not treated with insulin, was followed by recovery of uterine reactivity, reinforcing the hypothesis of the mobilization of Ca++ in discompensated alloxan-diabetic rats as a factor of variations on the sensibility of the tissues.
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PMID:[Uterine reactivity of alloxan-diabetic rats to oxytocin (author's transl)]. 56 68

Sections of neurosecretory cells fixed in glutaraldehyde and osmium tetroxide were studied by means of an EMMA-4 analytical microscope. Secretory granules in neurosecretory cells of the corpus cardiacum and of the brain, both in the desert locust Schistocerca and in the blowfly Calliphora, as well as neurosecretory granules in posterior pituitaries of the frog Rana and of the albino rat all contain a high concentration of calcium. A distinct sulphur peak was also a constant feature. In neurosecretory cells of the corpus cardiacum of Schistocerca the chromatin contained a high concentration of calcium. The mitochondria also contained much calcium, but part of this disappeared during preparation except when fixative and wash contained calcium chloride. By block staining with uranyl acetate most calcium is displaced from the mitochondria, whereas most of the calcium remains in the neurosecretory granules. Since the calcium peaks in spectra from neurosecretory granules appear of similar size, regardless of variations in the preparative procedure, this calcium must be firmly bound. The possible role of the calcium bound to the neurosecretory substance is discussed. The presence of sulphur in insect neurosecretory granules indicated the presence of a protein besides the hormone, i.e., an insect neurophysin.
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PMID:Calcium and sulphur in neurosecretory granules and calcium in mitochondria as determined by electron microscope x-ray microanalysis. 62 26


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