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

Recent data on the effects of neurohypophysial peptides at the cellular level are discussed with respect to the two basic processes involved in peptide hormone action--i.e., specific recognition of the information contained in the hormonal molecule and the transformation of this information into a stimulus leading to the final biological response. Four main aspects of this general problem are considered. A. Hormone-Receptor Interaction: Recent contributions in this field concern partial analysis of the three-dimensional conformation of oxytocin and vasopressin moleculal cells of the mammalian kidney. Conformational analysis of oxytocin and vasopressin molecules leads to the conclusion that, in solution, these peptides probably have a compact and highly stabilized three-dimensional configuration. Models have been proposed that provide a valuable clue to the interpretation of structure-activity relationships among natural hormones and many structural analogues. Binding studies with tritiated oxytocin and vasopressin have permitted determination of the kinetic parameters of hormone-receptor interaction in amphibian epithelial cells and mammalian kidney. B. Stimulus Generation: The nature of the primary stimulus generated by hormone-receptor interaction is still unknown. In the epithelial target cells of the amphibian skin and bladder and of the mammalian kidney, one of the first consequences of hormone-receptor interaction is the activation of membrane-bound adenylate cyclase. Analysis of the correlations between hormonal binding and adenylate cyclase activation suggests that activation is a function of receptor occupation rather than of the number of hormonal molecules interacting with the receptor per unit of time. On medullary adenylate cyclase of pig kidney, the relation between receptor occupancy and enzyme activation was found to be complex and nonlinear. The effects of several agents (calcium, nucleotides) on receptor occupancy and adenylate cyclase activation have been described. In mammalian uterus and other smooth muscle target cells, there is no evidence for direct involvement of cyclic AMP in the contractile response to oxytocin and other neurohypophysial peptides.
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PMID:Stimulus-response coupling in neurohypophysial peptide target cells. 17 91

Endometrial and myometrial tissues, obtained from Merino ewes on 5 different days of the estrous cycle, were incubated at 37 C in 30 ml of gassed (95% O2:5% CO2) Krebs-bicarbonate buffer containing, 0, 10, 100 or 1,000 muU/ml oxytocin. Aliquots of the medium were removed at 10 min intervals and examined for prostaglandin F2alpha (PGF2alpha) content by radioimmunoassay. Fresh-frozen (-70 C) samples of endometrial and myometrial tissue were homogenized in Tyrode's solution. Particulate fractions from each tissue, sedimenting between 1,000 X g for 10 min and 165,000 X g for 30 min, were prepared and assayed for [3H]oxytocin-binding activity. Endometrium incubated in vitro released PGF2alpha spontaneously and oxytocin enhanced this release in a dose-dependent manner. The degree of enhancement with low doses of oxytocin appeared to increase as estrus approached, reaching a maximum on the day of estrus. High-affinity binding sites (Kd = 5 to 7 X 10(-10) M) were found in both myometrium and endometrium. The number of high-affinity sites rose to a peak at estrus in both tissues but the binding capacity of endometrium was twice that of the myometrium at this time. Although both tissues released PGF2alpha during incubation, oxytocin enhanced release from endometrial tissue only. The results suggest that (i) the endometrium is a target for oxytocin, (ii) synthesis of PGF2alpha by the uterus may involve interaction between oxytocin and its endometrial receptors and (iii) ovarian steroids may influence uterine PG synthesis by regulating the availability of these receptors.
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PMID:Oxytocin-stimulated release of prostaglandin F2alpha from ovine endometrium in vitro: correlation with estrous cycle and oxytocin-receptor binding. 18 47

High affinity binding sites for 3[H] oxytocin have been demonstrated in particulate fractions from rat uterus and oviduct, myometrium from the sow, ewe and human, ewe endometrium, and mammary gland from the lactating rat. The binding activity has been localized to enriched plasma membrane fractions from the rat uterus and mammary gland; cells isolated from the mammary gland also bind oxytocin. The apparent dissociation constant (Kd) for the interaction of oxytocin with its binding sites in a variety of tissue preparations is in the nanomolar range. The concentration of oxytocin eliciting half-maximal contraction of the rat isolated uterus corresponds to the apparent Kd of oxytocin interaction with uterine particulate fractions. Binding is specific with respect to the target tissue or cell, as well as to the ligand. The affinity of binding sites for oxytocin analogues corresponds generally to their potencies as agonists or antagonists. Factors that affect the binding of oxytocin affect the biological response in the same way. For example, certain divalent metal ions, which increase oxytocin binding activity, enhance the sensitivity of the contractile response of the uterus and mammary gland to oxytocin. Estrogen administration, which increases the uterine binding of oxytocin, increases the sensitivity of the myometrium to oxytocin. The myometrium binds the most oxytocin at estrus and is most sensitive to oxtocin at that time. The dgree of stimulation by oxytocin of prostaglandin F2alpha synthesis by ewe endometrium is paralleled by an increased concentration of oxytocin binding sites. The marked increase in sensitivity to oxytocin of the rat uterus occurring on the day of parturition also is reflected by the amount of oxytocin bound by the uterus. Because of the many correlations between oxytocin binding and bioactivity, it appears that oxytocin binding sites on the plasma membrane of target cells constitute the recognition part of oxytocin receptors.
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PMID:Characterization of oxytocin receptors in the uterus and mammary gland. 19 1

Following a brief review of the preferred three-dimensional structured proposed for oxytocin in dimethylsulfoxide and in aqueous medium, the "cooperative model" for the biologically active conformation of oxytocin is discussed. An approach to conformation-activity analysis is described. The importance of determining the peptide backbone conformation and the functional contribution of peptide backbone and amino acid side chains to hormone receptor interactions are analyzed. Sites are proposed that are thought to be involved in the binding process of oxytocin to the smooth muscle receptor in rat uterus, as well as sites that are thought to be responsible for receptor activation.
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PMID:Indentification of sites in oxytocin involved in uterine receptor recognition and activation. 19 3

[3-Iodo-Tyr2]oxytocin (MIOT), [3,5-diiodo-Tyr2]oxytocin (DIOT), [3-iodo-Tyr2,Lys8]vasopressin (MILVP), [3,5-diiodo-Tyr2,Lys8]vasopressin (DILVP), [3-iodo-Tyr2,Arg8]vasopressin (MIAVP), and [3,5-diiodo-Tyr2,Arg8]vasopressin (DIAVP) were synthesized by iodination of the respective hormones, pruified, and characterized. All the monoiodo hormones had to be freshly prepared prior to bioassays, since on storage they gave rise to hormonal-like biological activity. The biological activities of these iodo analogues were measured in an adenylate cyclase assay employing neurohypophyseal hormone (NHH) sensitive bovine renal medullary membranes, and/or the rat oxytocic assay. In the cyclase assay, DIOT, DILVP, and DIAVP were inactive as agonists or antagonists. MIOT shows no agonistic activity in the renal cyclase system and uterus, but is a weak reversible inhibitor of oxytocin (OT) in both systems. When MIOT (10(-4) M) was preincubated with renal membranes for 10 min at 37 degrees C before addition of OT, it behaved as a noncompetitive inhibitor of NHH-stimulated adenylate cyclase. MILVP and MIAVP appear to be partial agonists with Km (half maximal response) 3 X 10(-6) and 3 X 10(-7) M, respectively, as determined in the cyclase assay. Upon preincubation with renal medullary membranes, MILVP (10(-6) M) behaves as a more potent noncompetitive inhibitor of OT than MIOT. Accordingly, iodo derivatives of NHH do not exhibit sufficient affinity to serve an specific ligands to measure OT, LVP, or AVP receptors in the uterus and kidney. Study of the specificity of inhibition produced by MIOT revealed that this analogue does not act selectively upon NHH receptors. Thus, MIOT modified adenylate cyclase systems which do not have NHH receptors, e.g., the PTH-sensitive adenylate cyclase in bovine renal cortex and the glucagon-sensitive adenylate cyclase in rat liver. DIOT, DILVP, and DIAVP were subjected to catalytic tritiation (employing carrier free tritium) and were converted to [3H]OT (25, 31, and 25 Ci/mmol), [3H]LVP (26 and 23 Ci/mmol), and [3H]AVP (17 Ci/mmol), respectively. These tritiated ligands have been successfully used to measure NHH receptor sites both in kidney and uterine membranes as described in other studies.
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PMID:Iodinated neurohypophyseal hormones as potential ligands for receptor binding and intermediates in synthesis of tritiated hormones. 19 53

Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.
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PMID:Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus. 20 80

The distribution of [3H]oxytocin binding sites among various subcellular fractions of rat myometrium paralleled the distribution of 5'-nucleotidase, a plasma membrane marker enzyme, but not of NADPH-cytochrome c reductase or succinate-cytochrome c reductase, which are endoplasmic reticulum and mitochondrial marker enzymes respectively. [3H]Oxytocin binding to the most enriched plasma membrane fraction showed the degree of selectivity with respect to hormone analogues that is expected for the oxytocin receptor. The binding of oxytocin to this fraction showed an apparent Kd of 1.98 X 10(-9) M and a capacity of 1.28 pmol mg-1. It is concluded that the oxytocin receptor is located on the plasma membrane of the smooth muscle cells of the rat uterus.
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PMID:Localization of the oxytocin receptor in the plasma membrane of rat myometrium. 20 28

The analysis of pA2 values for 1,2-substituted oxytocin analogues suggests a significant resonance effect of p-substituted groups in 2-tyrosine when the hormone binds to its uterus receptor, whereas the N-terminal amino group exerts less clearly characterized effects (participation of its lipophilicity and molecular volume can be assumed.
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PMID:Affinity of 1,2-substituted oxytocin analogues to the uterus receptor: Free-Wilson and Hansch analysis. 21 32

Specific binding of tritiated oxytocin to uterine receptors of pregnant rats increases dramatically at term and is maximal during labor. In mammary glands the increase in binding is gradual, reaching a maximum during the lactation period. Concomitant changes in the sensitivity of the uterus and mammary gland to oxytocin indicate that the receptor concentration is of functional significance. Oxytocin receptors, therefore, may regulate the response of the target organs to circulating oxytocin and thereby control the onset of labor and lactation. Ovarian steroids participate in the regulation of oxytocin receptors in a manner as yet unclarified.
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PMID:Oxytocin receptors: triggers for parturition and lactation? 22 72

Procedures and indications for nonstress fetal monitoring, oxytocin challenge tests, 24-hour measurement of urine estriols, ultrasound, and amniocentesis, five of the most widely used diagnostic tools for monitoring the fetus at risk, are reviewed. While none of these tests is completely accurate by itself, selective use of these tests improves the ability to diagnose placental insufficiency and to predict the ability of the fetus to survive outside the uterus. Complications may threaten the life of the fetus, but delivery can be timed to minimize the complications associated with prematurity. Overall, skilled medical management of underlying problems remains most important, while tests of placental insufficiency add valuable, but supplementary guidelines for overall management of the high-risk patient.
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PMID:High-risk pregnancy screening techniques: a nursing overview. 25 50


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