Oxytocin and vasopressin stimulate inositol phosphate production in human gestational myometrium and decidua cells

1986 ◽  
Vol 6 (7) ◽  
pp. 613-619 ◽  
Author(s):  
Michael P. Schrey ◽  
Alison M. Read ◽  
Philip J. Steer
Keyword(s):  
Arachidonic Acid ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Diacylglycerol Lipase ◽  
Inositol 1 ◽  
Inositol Phosphate Production ◽  
Acid Accumulation ◽  
Free Arachidonic Acid ◽  
Hydrolysis Of ◽  
Related Increase

The involvement of phosphoinositide hydrolysis in the action of oxytocin and vasopressin on the uterus was investigated in gestational myometrium and decidua cells by measuring the production of inositol phosphates. Both peptides stimulated a dose related increase in all three inositol phosphates in myometrium. This may be related to the control of sarcoplasmic Ca++ levels in the myometrium. Oxytocin and vasopressin also stimulated inositol 1-phosphate (IP) production in decidua cells. The hydrolysis of phosphatidylinositol by decidua homogenates exhibited a precursor-product relationship for diacylglycerol and arachidonic acid accumulation. Hence both peptides may mobilise free arachidonic acid, for prostaglandin biosynthesis, from decidua cell phosphoinositides by the sequential action of phospholipase C and diacylglycerol lipase.

Dopamine does not attenuate phosphoinositide hydrolysis in rat anterior pituitary cells

1986 ◽  
Vol 110 (3) ◽  
pp. 389-393 ◽  
Author(s):  
P. L. Canonico ◽  
W. D. Jarvis ◽  
A. M. Judd ◽  
R. M. MacLeod
Keyword(s):  
Anterior Pituitary ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Pituitary Cells ◽  
Anterior Pituitary Cells ◽  
Marked Diminution ◽  
Inositol Phosphate Production ◽  
Concomitant Reduction ◽  
Potent Agonist ◽  
Hydrolysis Of

ABSTRACT The hydrolysis of membrane phosphatidylinositol to yield [3H]labelled inositol phosphates by anterior pituitary cells was stimulated significantly by angiotensin II, TRH and neurotensin over a broad range of concentrations. These secretagogues also stimulated release of prolactin. Although the coincident incubation of dopamine with these agents resulted in a marked diminution of prolactin release, no concomitant reduction in inositol phosphate production was observed. In addition, bromocriptine, a potent agonist of dopamine, also proved ineffective in blunting stimulated phosphatidylinositol catabolism. Although it slightly inhibited basal rates of inositol tris-, bis- and monophosphate production, these results show that the secretagogue-mediated enhancement of phosphatidylinositol catabolism may be correlated with an increased release of prolactin and that the inhibition of hormone release produced by dopamine is not achieved by reducing basal or secretagogue-mediated inositol phosphate production. J. Endocr. (1986) 110, 389–393

scholarly journals The α1-adrenergic transduction system in hamster brown adipocytes. Release of arachidonic acid accompanies activation of phospholipase C

1988 ◽  
Vol 253 (1) ◽  
pp. 93-102 ◽  
Author(s):  
R J Schimmel
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Phospholipase C ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Neutral Lipids ◽  
Receptor Activation ◽  
Ionophore A23187 ◽  
Brown Adipocytes ◽  
Diacylglycerol Lipase

Previous studies of brown adipocytes identified an increased breakdown of phosphoinositides after selective alpha 1-adrenergic-receptor activation. The present paper reports that this response, elicited with phenylephrine in the presence of propranolol and measured as the accumulation of [3H]inositol phosphates, is accompanied by increased release of [3H]arachidonic acid from cells prelabelled with [3H]arachidonic acid. Differences between stimulated arachidonic acid release and formation of inositol phosphates included a requirement for extracellular Ca2+ for stimulated release of arachidonic acid but not for the formation of inositol phosphates and the preferential inhibition of inositol phosphate formation by phorbol 12-myristate 13-acetate. The release of arachidonic acid in response to phenylephrine was associated with an accumulation of [3H]arachidonic acid-labelled diacylglycerol, and this response was not dependent on extracellular Ca2+ but was partially prevented by treatment with the phorbol ester. The release of arachidonic acid was also stimulated by melittin, which increases the activity of phospholipase A2, by ionophore A23187, by lipolytic stimulation with forskolin and by exogenous phospholipase C. The arachidonic acid response to phospholipase C was completely blocked by RHC 80267, an inhibitor of diacylglycerol lipase, but this inhibitor had no effect on release stimulated with melittin or A23187 and inhibited phenylephrine-stimulated release by only 40%. The arachidonate response to forskolin was additive with the responses to either phenylephrine or exogenous phospholipase C. These data indicate that brown adipocytes are capable of releasing arachidonic acid from neutral lipids via triacylglycerol lipolysis, and from phospholipids via phospholipase A2 or by the sequential activities of phospholipase C and diacylglycerol lipase. Our findings also suggest that the action of phenylephrine to promote the liberation of arachidonic acid utilizes both of these reactions.

scholarly journals Gonadotropin releasing hormone stimulates the formation of inositol phosphates in rat anterior pituitary tissue

1985 ◽  
Vol 226 (2) ◽  
pp. 563-569 ◽  
Author(s):  
M P Schrey
Keyword(s):  
Anterior Pituitary ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Inositol Trisphosphate ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inositol 1 ◽  
Pituitary Tissue ◽  
Inositol Phosphate Production ◽  
Stimulation Of

The production of inositol phosphates in response to gonadotropin releasing hormone (GnRH) was studied in rat anterior pituitary tissue preincubated with [3H]inositol. Prelabelled paired hemipituitaries from prepubertal female rats were incubated in the presence or absence of GnRH in medium containing 10 mM-Li+ X Li+, which inhibits myo-inositol-1-phosphatase, greatly amplified the stimulation of inositol phosphate production by GnRH (10(-7) M) to 159, 198 and 313% of paired control values for inositol 1-phosphate, inositol bisphosphate and inositol trisphosphate respectively after 20 min. The percentage distribution of [3H]inositol within the phosphoinositides was 91.3, 6.3 and 2.4 for phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively and was unaffected by GnRH. The stimulation of inositol trisphosphate production by GnRH was evident after 5 min incubation, was dose-dependent with a half-maximal effect around 11 nM, and was not inhibited by removal of extracellular Ca2+. Elevation of cytosolic Ca2+ by membrane depolarization with 50 mM-K+ had no significant effect on inositol phosphate production. These findings are consistent with the hypothesis that GnRH action in the anterior pituitary involves the hydrolysis of phosphatidylinositol 4,5-bisphosphate. The resulting elevation of inositol trisphosphate may in turn lead to intracellular Ca2+ mobilization and subsequent stimulation of gonadotropin secretion.

scholarly journals Accumulation of inositol polyphosphate isomers in agonist-stimulated cerebral-cortex slices. Comparison with metabolic profiles in cell-free preparations

1989 ◽  
Vol 258 (1) ◽  
pp. 23-32 ◽  
Author(s):  
I H Batty ◽  
A J Letcher ◽  
S R Nahorski
Keyword(s):  
Cerebral Cortex ◽  
Inositol Phosphates ◽  
Periodate Oxidation ◽  
Chemical Degradation ◽  
Inositol Polyphosphate ◽  
Tissue Slices ◽  
Inositol 1 ◽  
Agonist Stimulation ◽  
Cortex Slices ◽  
Hydrolysis Of

1. Basal and carbachol-stimulated accumulations of isomeric [3H]inositol mono-, bis-, tris- and tetrakis-phosphates were examined in rat cerebral-cortex slices labelled with myo-[2-3H]inositol. 2. In control samples the major [3H]inositol phosphates detected were co-eluted on h.p.l.c. with Ins(1)P, Ins(4)P (inositol 1- and 4-monophosphate respectively), Ins(1,4)P2 (inositol 1,4-bisphosphate), Ins(1,4,5)P3 (inositol 1,4,5-tris-phosphate) and Ins(1,3,4,5)P4 (inositol 1,3,4,5-tetrakisphosphate). 3. After stimulation to steady state with carbachol, accumulation of each of these products was markedly increased. 4. Agonist stimulation, however, also evoked much more dramatic increased accumulations of a second [3H]inositol trisphosphate, which was co-eluted on h.p.l.c. with authentic Ins(1,3,4)P3 (inositol 1,3,4-trisphosphate) and of three further [3H]inositol bisphosphates ([3H]InsP2(s]. 5. Examination of the latter by chemical degradation by periodate oxidation and/or h.p.l.c. allowed identification of these as [3H]Ins(1,3)P2, [3H]Ins(3,4)P2 and [3H]Ins(4,5)P2 (inositol 1,3-, 3,4- and 4,5-bisphosphates respectively), which respectively accounted for about 22%, 8% and 3% of total [3H]InsP2 in extracts from stimulated tissue slices. 6. By using a h.p.l.c. method which clearly resolves Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 (inositol 1,3,4,6-tetrakisphosphate), only the former isomer could be detected in extracts from either control or stimulated tissue slices. Similarly, [3H]inositol pentakis- and hexakis-phosphates were not detectable either in the presence or absence of carbachol under the radiolabelling conditions described. 7. The catabolism of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 by cell-free preparations from cerebral cortex was also studied. 8. In the presence of Mg2+, [3H]Ins(1,4,5)P3 was specifically dephosphorylated via [3H]Ins(1,4)P2 and [3H]Ins(4)P to free [3H]inositol, whereas [3H]Ins(1,3,4)P3 was degraded via [3H]Ins(3,4)P2 and, to a lesser extent, via [3H]Ins(1,3)P2 to D- and/or L-[3H]Ins(1)P and [3H]inositol. 9. In the presence of EDTA, hydrolysis of [3H]Ins(1,4,5)P3 was greater than or equal to 95% inhibited, whereas [3H]Ins(1,3,4)P3 was still degraded, but yielded only a single [3H]InsP2 identified as [3H]Ins(1,3)P2. 10. The significance of these observations with cell-free preparations is discussed in relation to the proportions of the separate isomeric [3H]inositol phosphates measured in stimulated tissue slices.

Carbachol-induced desensitization of PLC-β pathway in rat myometrium: downregulation of Gqα/G11α

1998 ◽  
Vol 275 (3) ◽  
pp. C636-C645 ◽  
Author(s):  
Sandrine Lajat ◽  
Simone Harbon ◽  
Zahra Tanfin
Keyword(s):  
Binding Sites ◽  
Prolonged Exposure ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Initial Period ◽  
Kinase C ◽  
Inositol Phosphate Production ◽  
Muscarinic Binding Sites ◽  
Heterologous Desensitization ◽  
Delayed Phase

In the estrogen-treated rat myometrium, carbachol increased the generation of inositol phosphates by stimulating the muscarinic receptor-Gq/G11-phospholipase C-β3 (PLC-β3) cascade. Exposure to carbachol resulted in a rapid and specific (homologous) attenuation of the subsequent muscarinic responses in terms of inositol phosphate production, PLC-β3 translocation to membrane, and contraction. Refractoriness was accompanied by a reduction of membrane muscarinic binding sites and an uncoupled state of residual receptors. Protein kinase C (PKC) altered the functionality of muscarinic receptors and contributed to the initial period of desensitization. A delayed phase of the muscarinic refractoriness was PKC independent and was associated with a downregulation of Gqα/G11α. Atropine failed to induce desensitization as well as Gqα/G11α downregulation, indicating that both events involve active occupancy of the receptor. Prolonged exposure to A[Formula: see text] reduced subsequent A[Formula: see text] as well as carbachol-mediated inositol phosphate responses and similarly induced downregulation of Gqα/G11α. Data suggest that a decrease in the level of Gqα/G11α is subsequent to its activation and may account for heterologous desensitization.

scholarly journals G-proteins are not directly involved in the CD3-antigen-mediated production of inositol phosphates in HPB-ALL T-leukaemia cells expressing phospholipase C isoforms γ1 and β3

1993 ◽  
Vol 289 (2) ◽  
pp. 387-394 ◽  
Author(s):  
M Biffen ◽  
M Shiroo ◽  
D R Alexander
Keyword(s):  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
G Protein ◽  
G Proteins ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Cross Linking ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Inositol Phosphate Production

The possible involvement of G-proteins in T cell antigen-receptor complex (TCR)-mediated inositol phosphate production was investigated in HPB-ALL T-cells, which were found to express the phospholipase C gamma 1 and beta 3 isoforms. Cross-linking the CD3 antigen on streptolysin-O-permeabilized cells stimulated a dose-dependent increase in inositol phosphate production, as did addition of guanosine 5′-[gamma-thio]triphosphate (GTP[S]) or vanadate, a phosphotyrosine phosphatase inhibitor. It was possible, therefore, that the CD3-antigen-mediated production of inositol phosphates was either via a G-protein-dependent mechanism or by stimulation of protein tyrosine phosphorylation. The CD3-induced inositol phosphate production was potentiated by addition of vanadate, but not by addition of GTP[S]. Guanosine 5′-[beta-thio]diphosphate (GDP[S]) inhibited the rise in inositol phosphates induced by GTP[S], vanadate or cross-linking the CD3 antigen. The increase in protein tyrosine phosphorylation stimulated by vanadate or the OKT3 monoclonal antibody was not observed in the presence of GDP[S], showing that in permeabilized HPB-ALL cells, GDP[S] inhibits the actions of tyrosine kinases as well as G-protein function. Addition of either ADP[S] or phenylarsine oxide inhibited CD3- and vanadate-mediated increases in both tyrosine phosphorylation and inositol phosphate production, but did not inhibit GTP[S]-stimulated inositol phosphate production. On the other hand, pretreatment of cells with phorbol 12,13-dibutyrate inhibited subsequent GTP[S]-stimulated inositol phosphate production but did not inhibit significantly inositol phosphate production stimulated by either OKT3 F(ab')2 fragments or vanadate. Our results are consistent with the CD3 antigen stimulating inositol phosphate production by increasing the level of protein tyrosine phosphorylation, but not by activating a G-protein.

scholarly journals Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands

1983 ◽  
Vol 216 (3) ◽  
pp. 633-640 ◽  
Author(s):  
C P Downes ◽  
M M Wusteman
Keyword(s):  
Molecular Mechanisms ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Muscarinic Agonist ◽  
Parotid Glands ◽  
Muscarinic Agonists ◽  
Inositol 1 ◽  
Inositol 1,4,5 Trisphosphate ◽  
Rat Parotid ◽  
Phosphatidylinositol 4

The molecular mechanisms underlying the ability of muscarinic agonists to enhance the metabolism of inositol phospholipids were studied using rat parotid gland slices prelabelled with tracer quantities of [3H]inositol and then washed with 10 mM unlabelled inositol. Carbachol treatment caused rapid and marked increases in the levels of radioactive inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,4,5-trisphosphate and an accumulation of label in the free inositol pool. There were much less marked changes in the levels of [3H]phosphatidylinositol, [3H]phosphatidylinositol 4-phosphate and [3H]phosphatidylinositol 4,5-bisphosphate. At 5 s after stimulation with carbachol there were large increases in [3H]inositol 1,4-bisphosphate and [3H]inositol 1,4,5-trisphosphate, but not in [3H]inositol 1-phosphate. After stimulation with carbachol for 10 min the levels of radioactive inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate greatly exceeded the starting level of radioactivity in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively. When carbachol treatment was followed by addition of sufficient atropine to block all the muscarinic receptors the radioactive inositol phosphates rapidly returned towards control levels. The carbachol-evoked changes in radioactive inositol phosphate and phospholipid levels were blocked in the presence of 2,4-dinitrophenol (an uncoupler of oxidative phosphorylation). The results suggest that muscarinic agonists stimulate a polyphosphoinositide-specific phospholipase C and that these lipids are continuously replenished from the labelled phosphatidylinositol pool. [3H]Inositol 1-phosphate in the stimulated glands probably arises via hydrolysis of inositol 1,4-bisphosphate and not directly from phosphatidylinositol.

Phosphoranylation de polyols: Voie d'accès aux phosphates d'intérêt biologique. I. Cas du myo-inositol

1988 ◽  
Vol 66 (12) ◽  
pp. 2965-2974 ◽  
Author(s):  
Brigitte Duthu ◽  
Douraid Houalla ◽  
Robert Wolf
Keyword(s):  
Acid Hydrolysis ◽  
Inositol Phosphates ◽  
Original Method ◽  
Inositol 1 ◽  
Reaction Proceeds ◽  
Hydrolysis Of

An original method for the phosphorylation of an unprotected myo-inositol is described, which yields several myo-inositol phosphates at the same time. The reaction proceeds via a partial or complete phosphoranylation of the cyclitol by means of the aminobicyclophosphane 8, followed by oxidation of the resulting bicyclophosphoranes bearing a P—H bond and acid hydrolysis of the neutral phosphates thus formed. In the case of the tris-phosphoranylation we identified, among the HPLC fractions, the myo-inositol-1,2-(cycl)phosphate 22, the myo-inositol-1-phosphate 23, and the myo-inositol-2-phosphate 24.

scholarly journals Arachidonic acid is functioning as a second messenger in activating the Ca2+ entry process on H1-histaminoceptor stimulation in DDT1 MF-2 cells

1995 ◽  
Vol 305 (3) ◽  
pp. 859-864 ◽  
Author(s):  
L van der Zee ◽  
A Nelemans ◽  
A den Hertog
Keyword(s):  
Arachidonic Acid ◽  
Extracellular Space ◽  
Channel Blocker ◽  
Vas Deferens ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messenger ◽  
Slow Decline ◽  
K Current ◽  
Ca2 Channels

This study was carried out to identify the cellular component activating the histamine-stimulated Ca2+ entry in vas-deferens-derived DDT1 MF-2 cells. H1-histaminoceptor stimulation resulted in a rise in intracellular Ca2+ concentration, caused by Ca2+ release from inositol phosphate-sensitive Ca2+ stores and Ca2+ entry from the extracellular space, accompanied by a transient Ca(2+)-activated outward K+ current. The histamine-evoked K+ current was still observed after preventing inositol phosphate-induced Ca2+ mobilization by intracellularly applied heparin. This current was activated by Ca2+ entry from the extracellular space, because it was abolished in the presence of the Ca(2+)-channel blocker La3+ or under Ca(2+)-free conditions. H1-histaminoceptor-activated Ca2+ entry was also observed in the presence of intracellularly applied Ins(1,4,5)P3 and Ins(1,3,4,5)P4, depleting their respective Ca2+ stores and pre-activating the inositol phosphate-regulated Ca2+ entry. Thus the ability of histamine to activate Ca2+ entry independently of Ca2+ mobilization and the formation of inositol phosphates suggests that another component is involved to initiate the Ca(2+)-entry process. It was observed that H1-histaminoceptor stimulation resulted in a pronounced release of arachidonic acid (AA) in DDT1 MF-2 cells. Exogenously applied AA induced a concentration-dependent increase in internal Ca2+ due to activation of Ca2+ entry from the extracellular space. Slow inactivation of the AA-sensitive Ca2+ channels is suggested by the slow decline in Ca2+ entry. In accord, the histamine-induced Ca2+ entry was not observed with AA-pre-activated Ca2+ channels. Inhibition of the lipoxygenase and cyclo-oxygenase pathway did not affect the AA-induced Ca2+ and the concomitant K+ current were decreased in the presence of AA and caused by Ca2+ mobilization from internal stores. Blocking this internal Ca2+ release by heparin, in the presence of AA, resulted in abolition of the histamine-induced Ca(2+)-regulated K+ current. These observations show that AA, released on H1-histaminoceptor stimulation in DDT1 MF-2 cells, is functioning as a second messenger to activate plasma-membrane Ca2+ channels promoting Ca2+ entry from the extracellular space.

scholarly journals Muscarinic-receptor stimulation enhances polyphosphoinositide breakdown in guinea-pig ileum smooth muscle

1984 ◽  
Vol 223 (2) ◽  
pp. 527-531 ◽  
Author(s):  
M C Sekar ◽  
B D Roufogalis
Keyword(s):  
Guinea Pig ◽  
Muscarinic Receptor ◽  
Longitudinal Muscle ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Exchange Chromatography ◽  
Guinea Pig Ileum ◽  
Receptor Stimulation ◽  
Inositol 1 ◽  
Stimulation Of

Muscarinic-receptor stimulation by 0.1 mM-carbachol in longitudinal muscle of the guinea-pig ileum increases the incorporation of [3H]inositol into inositol-containing phospholipid. This effect was blocked by 16 microM-atropine. After 60 min incubation, carbachol increased the accumulation of total inositol phosphates 20-fold in the presence of 10 mM-Li+. Less than 20% of the total inositol phosphate corresponded to inositol 1-phosphate by ion-exchange chromatography, whereas of the remainder about two-thirds corresponded to inositol bisphosphate and one third to inositol trisphosphate. It is concluded that stimulation of muscarinic receptors in guinea-pig ileum enhances breakdown of polyphosphoinositides, suggesting that this may be a primary event associated with Ca2+ mobilization in the guinea-pig ileum.

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