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. Ca reversal was reported on the longitudinal smooth muscle of rat uterus and the fundic part of the circular smooth muscle of guinea pig stomach; that is, addition of Ca ion to the Ca-free bathing solution in which the muscle is contracting to oxytocin or carbachol, respectively, relaxes the muscle. 2. We tested whether this inhibitory action of Ca ion is seen in other smooth muscles including vascular, air way, gastric and genital smooth muscles. 3. We found that Ca reversal was observed in the smooth muscle of rat thoracic aorta contracted by norepinephrine or by a phorbol ester, TPA, guinea pig tracheal smooth muscle contracted to carbachol, fundic smooth muscle of rat stomach to carbachol, corporal and antral smooth muscle of guinea pig stomach to carbachol and rat vas deferens to norepinephrine. 4. Ca reversal was observed not only when the muscle contracted by an agonist of the surface receptor such as oxytocin, norepinephrine or carbachol but also by a phorbol ester that is believed to cause contraction in the cell by activating phosphorylation. 5. Thus, we conclude that Ca reversal is a universal phenomenon in smooth muscles.
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PMID:Calcium reversal, relaxation by calcium ion of various smooth muscles contracted by carbachol, norepinephrine or a phorbol ester in calcium-ion free medium. 205 Feb 84

1. Isolated nerve endings from rat neurohypophyses were permeabilized with digitonin in order to gain access to the cytoplasm. Release of vasopressin (AVP), oxytocin and the neurophysins was studied under different experimental conditions. 2. Hormone release, which occurred by exocytosis, was Ca2+ dependent. Half-maximal release was observed at ca. 1.7 microM-Ca2+ in contrast to ca. 300 microM for K+-induced hormone secretion from non-permeabilized neurosecretosomes. 3. Release also occurred when the neurosecretosomes were challenged with Ca2+ 20 min after digitonin treatment. This suggests that the isolated nerve endings remain permeable after treatment with digitonin. 4. Although hormone release was potentiated in the presence of ATP, and to a lesser extent with guanosine triphosphate (GTP), secretion occurred in the absence of nucleotides. 5. Replacement of K+ as the major cation by Na+ did not modify the secretory response to a Ca2+ challenge. Release, although reduced, still occurred when KCl was replaced by sucrose. 6. Compared to glutamate, Cl-, Br- and I- did not modify the Ca2+-independent release. This release was increased in the presence of SCN-. The order of effectiveness of the anions studied in inhibiting the Ca2+-dependent release was glutamate less than Br- = Cl- = I- less than SCN-. 7. Increasing the osmolarity of the perfusate inhibited the Ca2+-dependent release of AVP and oxytocin. 8. Vincristine, which binds to microtubules, had no effect on the secretory process. 9. Ca2+ dependent AVP release was partially inhibited by the calmodulin antagonist trifluoroperazine. 10. Hormone release was potentiated by the protein kinase C activator, 4-beta-phorbol 12-myristate acetate (TPA). 11. Whereas 0.2 microM-Ca2+ induced a barely significant increase in AVP release, inositol 1,4,5-triphosphate, in the continued presence of 0.2 microM-Ca2+, produced a large secretory response. 12. 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS), an inhibitor of Cl- permeability, reduced the Ca2+-dependent AVP release. 13. Carbonyl cyanide m-chlorophenylhydrazone (CCCP), which reduces the transmembrane potential of isolated neurohypophysial granules, inhibited the Ca2+-dependent hormone secretion. 14. Maximal hormone release occurred at pH 6.6. 15. It is concluded that the permeabilized neurosecretosomes represent an excellent model for studying the minimal requirements for neurosecretion.
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PMID:Requirements for hormone release from permeabilized nerve endings isolated from the rat neurohypophysis. 245 Oct

In myometrium from pregnant rats, 100 nM-TPA elevated resting tension and initially slightly enhanced the contraction induced by 138 mM-KCl. After 20 min this force development significantly declined. In saponin-treated skinned myometrial cells from pregnant rats, 100 nM-TPA enhanced the contraction induced by 0.3 microM-Ca2+, but reduced that induced by 1 microM-Ca2+. These findings suggest that the excitatory and inhibitory actions of TPA on the myometrium are probably due to its action on the contractile proteins. In myometrium from non-pregnant rats, TPA affected neither the resting tension, nor the amplitude of the evoked contractions, nor the Ca2+-induced contractions in skinned myometrium. While TPA only affected tension development in pregnant rats, both 1 mM-carbachol and 90 nM-oxytocin induced a tonic contraction in Ca-free solution independently of the hormonal status of the rats. The latter finding makes it unlikely that activation of protein kinase C is involved in the agonist-induced tonic force development in Ca-free solution.
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PMID:TPA- and agonist-induced force development in myometrium from pregnant and non-pregnant rats. 291 51

The effect of arginine vasopressin (AVP) on protein phosphorylation in rat hippocampal synaptic plasma membranes (SPM) was examined. With a crude SPM preparation, AVP (10(-8)-10(-5) M) stimulated phosphorylation of a number of proteins which included a brain-specific protein of 48 kDa called B50 or protein F1, which is thought to be related to synaptic plasticity. Equimolar levels of oxytocin also stimulated B50/F1 phosphorylation. AVP and oxytocin at higher concentrations (10(-4)-10(-3) M) reduced SPM protein phosphorylation. When SPM was treated with both AVP and oxytocin, the effects were not additive; on the other hand, the effects of the phorbol ester (TPA) and AVP were additive. With SPM, partially purified by sucrose density centrifugation, only the inhibitory effect of AVP on B50/F1 phosphorylation was seen. These results suggest that AVP and oxytocin stimulation of B50/F1 phosphorylation requires cellular factors which are removed from SPM during membrane purification. In contrast, the inhibitory mechanism triggered by AVP and oxytocin appears to be associated with, or an integral part of, the synaptic membrane itself. Because the effects on membrane protein phosphorylation with maximal amounts of AVP and oxytocin were not additive, they must bind to the same sites on the membrane. This conclusion is supported by the additivity of the effects of AVP and phorbol ester, since the phorbol ester can act directly on the kinase and does not require a membrane recognition site.
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PMID:Protein phosphorylation in rat hippocampal synaptic plasma membranes in response to neurohypophyseal peptides. 379 Sep 90

The bovine CL is one of the sites for the production of prostaglandins (PG). Although many in vitro models, mainly using dispersed luteal cell incubations, have shown the variety of CL responses to PGs (luteotropic, no effect, or luteolytic), the functional role of luteal PGs in cattle remains to be elucidated. Therefore, the aim of the present study was to examine the effects of PGs with respect to progesterone (P4) and oxytocin (OT) release from the bovine CL in vitro (Days 8-12 of the estrous cycle) via a microdialysis system (MDS), in which intact cell-to-cell contact exists. Thirty-minute perfusion with PGF2 alpha, PGE2, and PGI2 (10(-10)-10(-5) M) induced significant, but different, acute effects. PGF2 alpha and PGE2 clearly stimulated hormone (P4 and OT) release, while PGI2 slightly inhibited hormone secretion during infusion at low doses but stimulated secretion at 10(-6) and 10(-5) M concentrations. Additionally, catabolized PGF2 alpha and PGI2 (13,14-dihydro-15-keto-PGF2 alpha [PGFM] and 6-keto-PGF1 alpha, respectively) induced responses different from those of the original PGs; both PGFM and 6-keto-PGF1 alpha at low doses weakly inhibited P4 release, but at 10(-5) M concentration stimulated release. Phorbol 12-myristate 13-acetate (TPA), a potent stimulator of the protein kinase C (PKC) system in bovine luteal cells, stimulated P4 and OT release when administered alone. Pre-exposure with TPA (10(-9) M) for 2.5 h resulted in an increase in the stimulative potency of PGF2 alpha and PGI2, but not of PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute actions of prostaglandin F2 alpha, E2, and I2 in microdialyzed bovine corpus luteum in vitro. 837 69

Vascular endothelial growth factor (VEGF) is the most important factor in the regulation of angiogenesis. Associated with luteinisation and formation of corpus luteum (CL) are alterations in luteal vascularity. The aim of the study was to test under in vitro conditions the stimulation of VEGF and progesterone (P) secretion of bovine granulosa cells by LH, IGF1 (insulin like growth factor) or by factors known to be produced by luteinised granulosa cells or in the early CL. Localisation of VEGF protein in preovulatory follicle and early CL were achieved by immunohistochemistry. LH and IGF1 stimulated dose dependently and significantly P and VEGF when tested alone. Both hormones added simultaneously had clear additive and even more interesting far greater (synergistic) effects on P with LH (0.1 ng/ml) plus 5 or 10 ng IGF1. In contrast, VEGF was stimulated only additively with 0.1 ng/ml of LH plus 5 or 10 ng IGF1. But with the higher dose of LH (1 ng/ml) additionally to the additive effect a tendency for a synergistic action (which was significant with 1 ng LH plus 5 ng IGF1/ml) was observed. Endothelin, oxytocin, progesterone, atrial natiuretic peptide, angiotensin II, prostaglandin F2 alpha alpha, prostaglandin E2, cortisol, fibroblast growth factor 1 and 2 and growth hormone showed no effect neither on P nor on VEGF. Tumour necrosis factor alpha (TNF alpha) stimulated (P < 0.05) VEGF with 10 or 100 ng/ml but not P. TPA (12-0 tetra decaenoyl-phorbol-13-acetate) or Ca2+ ionophore did not show a stimulatory effect in contrast to forskolin which increased P and VEGF secretion dose dependently. The VEGF protein was localised in follicle (granulosa cells, theca cells and some endothelial cells) and early (about 24 h after ovulation) CL (granulosa-lutein cells and endothelial cells). The same signalling pathway by stimulation of cAMP production and proteinkinase A activation for luteinisation and neo-vascularisation demonstrates a close temporal and spatial relationship of these normal physiological processes.
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PMID:Stimulatory and synergistic effects of luteinising hormone and insulin like growth factor 1 on the secretion of vascular endothelial growth factor and progesterone of cultured bovine granulosa cells. 1140 98

In the bovine corpus luteum (CL) phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) protein in response to prostaglandin F2alpha (PGF2alpha) is correlated with the secretion of oxytocin. The present study was conducted to 1) examine the intracellular translocation characteristics of wild-type and mutant forms of a green fluorescent protein (GFP)-conjugated MARCKS (MARCKS-GFP) after PGF2alpha treatment and 2) evaluate PGF2alpha-induced temporal changes in MARCKS-GFP and actin cortex associated with exocytosis of oxytocin. In experiment 1, cells of the bovine CL were cultured on coverslips overnight. Then, wild-type and mutant MARCKS-GFP constructs were transfected separately into cells and expression was detected through fluorescence microscopy. Forty-eight hours after transfection, cells were treated with vehicle, PGF2alpha (56 nM), or a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA], 1 microM). Treatment of cells expressing wild-type MARCKS-GFP with PGF2alpha and TPA resulted in translocation of MARCKS from the plasma membrane to the cytoplasm within 2.5 min. Phosphorylation mutant MARCKS-GFP (m3) protein was localized on the plasma membrane, and treatments did not cause its translocation to the cytoplasm. Myristoylation mutant MARCKS-GFP (G2A) was observed solely in the cytoplasm, and no changes were detected in the intracellular location of this mutant MARCKS after treatment. In experiment 2, luteal cells were transfected with one of the three MARCKS-GFP constructs. Cells were then fixed and probed sequentially for oxytocin and filamentous actin. Results revealed that only wild-type MARCKS-GFP transfected large luteal cells contained advanced signs of exocytosis (peripheral movement of oxytocin vesicles; shorter actin filaments) with translocation of MARCKS-GFP from membrane to cytoplasm in response to PGF2alpha treatment. These data demonstrate that phosphorylation of membrane-bound MARCKS protein is requisite for exocytosis of oxytocin to occur in bovine large luteal cells.
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PMID:Spatiotemporal interactions of myristoylated alanine-rich C kinase substrate (MARCKS) protein with the actin cytoskeleton and exocytosis of oxytocin upon prostaglandin F2alpha stimulation of bovine luteal cells. 1293 Jul 25

Endothelin-1 (ET-1) and tumor necrosis factor-alpha (TNFalpha) participate in the cascade of luteolysis. Thus, in the present study the interactions of ET-1 and TNFalpha with prostaglandin F(2alpha) (PGF(2alpha)) on the release of progesterone and oxytocin (OT) within the corpus luteum (CL) were investigated. A microdialysis system (MDS) was surgically implanted in ovine CL (one MDS line/CL; 5-10 lines/ewe) formed after super-ovulation. A 4-h perfusion with PGF(2alpha) (0.01-1 micromol l (-1)) induced no clear effect on progesterone release, but acutely stimulated OT release in a dose-dependent manner. A perfusion of PGF(2alpha) (1 micromol l (-1)) increased ET-1 release over a period of 12 h. Two perfusions of ET-1 (0.1 micromol l(-1)) or a perfusion of ET-1 followed by TNFalpha (200 ng ml(-1)) decreased progesterone release (56-64% at 36-48 h). When the CL were pre-perfused with PGF(2alpha) (1 micromol l(-1)), two consecutive perfusions of ET-1 decreased progesterone release more rapidly. Similarly, a pre-perfusion with PGF(2alpha) followed by consecutive perfusions of ET-1 and then TNFalpha rapidly decreased progesterone release, with the inhibition most pronounced (35%) at 36-48 h. The simultaneous infusion of ET-1 with PGF(2alpha) induced a rapid decrease in progesterone release (36% at 36-48 h). In a further study, the possible second messenger systems involved in PGF(2alpha) action on the release of progesterone, OT and ET-1 were investigated. A perfusion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 10 micromol l(-1)), A23187 (10 micromol l(-1)), or PGF(2alpha) + A23187 increased progesterone release during infusion, but decreased it after perfusion. All treatments induced a massive release of OT during infusion, and increased ET-1 release after infusion. These results show that ET-1 is capable of suppressing progesterone release in the PGF(2alpha)-primed ovine CL in vivo and thus ET-1 works as a local luteolysin together with PGF(2alpha) during the process of functional luteolysis. During structural luteolysis, TNFalpha may interact with PGF(2alpha) and ET-1 to cause a rapid drop in progesterone release and accelerate the process of luteolysis. This result supports the contention that ET-1 and TNFalpha interact with PGF(2alpha) as local luteolytic mediators in the ewe as previously suggested.
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PMID:Local interaction of prostaglandin F 2alpha with endothelin-1 and tumor necrosis factor-alpha on the release of progesterone and oxytocin in ovine corpora lutea in vivo: a possible implication for a luteolytic cascade. 1505 76