scholarly journals Luteinizing hormone stimulates the formation of inositol trisphosphate and cyclic AMP in rat granulosa cells. Evidence for phospholipase C generated second messengers in the action of luteinizing hormone

1986 ◽  
Vol 238 (2) ◽  
pp. 597-604 ◽  
Author(s):  
J S Davis ◽  
L L Weakland ◽  
L A West ◽  
R V Farese
Keyword(s):  
Lipid Metabolism ◽  
Luteinizing Hormone ◽  
Cyclic Amp ◽  
Granulosa Cells ◽  
Cyclic Gmp ◽  
Time Course ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Inositol Trisphosphate

The following studies were conducted to determine whether luteinizing hormone (LH), a hormone which increases cellular levels of cyclic AMP, also provokes increases in ‘second messengers’ derived from inositol lipid metabolism (i.e. inositol phosphates and diacylglycerol). Rat granulosa cells isolated from mature Graafian follicles were prelabelled for 3 h with myo-[2-3H]inositol. LH provoked rapid (5 min) and sustained (up to 60 min) increases in the levels of inositol mono-, bis, and trisphosphates (IP, IP2 and IP3, respectively). Time course studies revealed that IP3 was formed more rapidly than IP2 and IP following LH treatment. The response to LH was concentration-dependent with maximal increases at LH concentrations of 1 microgram/ml. LiCl (2-40 mM) enhanced the LH-provoked accumulation of all [3H]inositol phosphates, presumably by inhibiting the action of inositol phosphate phosphatases. The effectiveness of LH, however, was dependent on the concentration of lithium employed; maximal increases in IP were observed at 10 mM-LiCl, whereas maximal increases in IP2 and IP3 were observed at 20 mM- and 40 mM-LiCl, respectively. The stimulatory effects of LH on inositol phosphate and progesterone accumulation were also compared with changes in cyclic nucleotide levels. LH rapidly increased levels of inositol phosphates, progesterone and cyclic AMP, but transiently reduced levels of cyclic GMP. These results demonstrate that LH increases both cyclic AMP and inositol trisphosphate (and presumably diacylglycerol) in rat granulosa cells. Our findings suggest that two messenger systems exist to mediate the action of LH in granulosa cells.

Involvement of second messengers and protein phosphorylation in astrocyte swelling

1992 ◽  
Vol 70 (S1) ◽  
pp. S362-S366 ◽  
Author(s):  
A. S. Bender ◽  
J. T. Neary ◽  
M. D. Norenberg
Keyword(s):  
Cyclic Amp ◽  
Protein Phosphorylation ◽  
Volume Regulation ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Astrocyte Swelling ◽  
Regulatory Processes ◽  
Intracellular Signals ◽  
Dependent Protein

In a hypoosmotic model of astrocyte swelling, we found that Ca2+ and intracellular signals such as diacylglycerol and inositol phosphate, as well as protein phosphorylation systems, are implicated in the generation and (or) modulation of volume regulatory processes. Cyclic AMP, which also has a significant effect on astrocyte volume regulation, in addition influences some of these second messengers.Key words: astrocyte, Ca2+-dependent protein kinases, Ca2+ influx, cell volume, cyclic AMP, inositol phosphates, protein phosphorylation.

scholarly journals Inositol phosphate formation in fMet-Leu-Phe-stimulated human neutrophils does not require an increase in the cytosolic free Ca2+ concentration

1985 ◽  
Vol 229 (2) ◽  
pp. 361-367 ◽  
Author(s):  
F Di Virgilio ◽  
L M Vicentini ◽  
S Treves ◽  
G Riz ◽  
T Pozzan
Keyword(s):  
Time Course ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Inositol Trisphosphate ◽  
Human Neutrophils ◽  
Chemotactic Peptide

The accumulation of inositol phosphates in myo-[3H]inositol-labelled human neutrophils stimulated with the chemotactic peptide fMet-Leu-Phe was measured. The challenge with the chemotactic peptide caused the generation of inositol monophosphate (InsP), inositol bisphosphate (InsP2) and inositol trisphosphate (InsP3). The formation of the three inositol phosphates followed a differential time course: InsP3 accumulated very rapidly and transiently, whereas InsP increased steadily for more than 2 min. Inositol phosphate formation was only partially decreased by procedures which prevented the fMet-Leu-Phe-dependent increase of cytosolic free Ca2+ concentration.

Inositol trisphosphate is involved in norepinephrine- but not in hypoxia-induced pulmonary arterial contraction

1993 ◽  
Vol 264 (2) ◽  
pp. L160-L164 ◽  
Author(s):  
N. Jin ◽  
C. S. Packer ◽  
D. English ◽  
R. A. Rhoades
Keyword(s):  
Time Course ◽  
Inositol Phosphates ◽  
Second Messengers ◽  
Acute Hypoxia ◽  
Inositol Trisphosphate ◽  
Pulmonary Arteries ◽  
Signal Transduction Pathway ◽  
Pulmonary Vasoconstriction ◽  
Arterial Contraction ◽  
Pulmonary Arterial

The role that second messengers play in pulmonary vasoconstriction is not understood. The purpose of this study was to directly measure inositol phosphates in isolated pulmonary arterial preparations before and during norepinephrine (NE) stimulation and acute hypoxia. Rat main pulmonary arteries were isolated and incubated with myo-[3H]-inositol. After incubation, control tissue was stimulated with 0.5 microM NE or 30 mM KCl. Test preparations were precontracted with 30 mM KCl and then exposed to hypoxia. Samples were homogenized and applied to a high-pressure liquid chromatography column for analysis of inositol phosphates. Results show that inositol trisphosphate (IP3) increases twofold at 5 s following NE stimulation. Thirty micromolars of KCl results in a slight but significant increase in IP3 formation at 5 min following the stimulation. Phentolamine inhibits the KCl-induced increase in IP3 formation, whereas A23187 has no effect on IP3 levels. Hypoxia caused a biphasic contraction in the precontracted isolated rat pulmonary artery. IP3 levels did not change during the hypoxic period. In conclusion, NE causes a rapid increase in IP3 formation consistent with the time course of production of an excitation-contraction coupling second messenger. However, inositol trisphosphate is not involved in the signal transduction pathway leading to pulmonary arterial contraction induced by hypoxia.

scholarly journals Activation of muscarinic receptors in PC12 cells. Correlation between cytosolic Ca2+ rise and phosphoinositide hydrolysis

1986 ◽  
Vol 234 (3) ◽  
pp. 555-562 ◽  
Author(s):  
L M Vicentini ◽  
A Ambrosini ◽  
F Di Virgilio ◽  
J Meldolesi ◽  
T Pozzan
Keyword(s):  
Cyclic Amp ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Inositol Trisphosphate ◽  
Phosphodiesterase Inhibitors ◽  
Receptor Activation ◽  
Phosphoinositide Hydrolysis ◽  
Dibutyryl Cyclic Amp ◽  
Permeabilized Cells ◽  
Concentration Curves

The intracellular signals generated by carbachol activation of the muscarinic receptor [release of inositol phosphates as a consequence of phosphoinositide hydrolysis and rise of the cytosolic Ca2+ concentration ([Ca2+]i, measured by quin2)] were studied in intact PC12 pheochromocytoma cells that had been differentiated by treatment with nerve growth factor. When measured in parallel samples of the same cell preparation 30 s after receptor activation, the release of inositol trisphosphate and of its possible metabolites, inositol bis- and mono-phosphate, and the [Ca2+]i rise were found to occur with almost superimposable carbachol concentration curves. At the same time carbachol caused a decrease in the radioactivity of preloaded phosphatidylinositol 4,5-bisphosphate, the precursor of inositol trisphosphate. Neither the inositol phosphate nor the [Ca2+]i signal was modified by preincubation of the cells with either purified Bordetella pertussis toxin or forskolin, the direct activator of adenylate cyclase. Both signals were partially inhibited by dibutyryl cyclic AMP, especially when the nucleotide analogue was applied in combination with the phosphodiesterase inhibitors RO 201724 and theophylline. The latter drug alone profoundly inhibited the carbachol-induced [Ca2+]i rise, with only minimal effect on phosphoinositide hydrolysis. Because of the diverging results obtained with forskolin on the one hand, dibutyryl cyclic AMP and phosphodiesterase inhibitors on the other, the effects of the latter drugs are considered to be pharmacological, independent of the intracellular cyclic AMP concentration. Two further drugs tested, mepacrine and MY5445, inhibited phosphoinositide hydrolysis at the same time as the 45Ca2+ influx stimulated by carbachol. Taken together, our results concur with previous evidence obtained with permeabilized cells and cell fractions to indicate phosphatidylinositol 4,5-bisphosphate hydrolysis and [Ca2+]i rise as two successive events in the intracellular transduction cascade initiated by receptor activation. The strict correlation between the carbachol concentration curves for inositol trisphosphate generation and [Ca2+]i rise, and the inhibition by theophylline of the Ca2$ signal without major effects on inositol phosphate generation, satisfy important requirements of the abovementioned interpretation.

Adrenergic stimulation of inositol phosphate accumulation in tracheal epithelium

1989 ◽  
Vol 66 (1) ◽  
pp. 504-508 ◽  
Author(s):  
T. Bainbridge ◽  
R. D. Feldman ◽  
M. J. Welsh
Keyword(s):  
Adrenergic Receptor ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Receptor Activation ◽  
Adrenergic Stimulation ◽  
Cl Secretion ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation ◽  
Stimulation Of

To determine whether inositol phosphates are important second messengers in the regulation of Cl- secretion by airway epithelia, we examined the relationship between inositol phosphate accumulation and Cl- secretion in response to adrenergic agonists. We found that epinephrine stimulated Cl- secretion and inositol phosphate accumulation with similar concentration dependence. Although isoproterenol stimulated Cl- secretion, there was no effect of beta-adrenergic receptor activation on inositol phosphate accumulation. In contrast, alpha 1-adrenergic receptor activation stimulated inositol phosphate accumulation but failed to induce Cl- secretion. Another Cl- secretagogue, prostaglandin E1, also failed to stimulate inositol phosphate accumulation. These data suggest that inositol phosphate accumulation is neither sufficient nor required for stimulation of Cl- secretion in cultured canine tracheal epithelial cells.

Guinea pig anaphylaxis: Time course of changes in cyclic AMP and cyclic GMP

Life Sciences ◽  
1977 ◽  
Vol 21 (9) ◽  
pp. 1365-1372 ◽  
Author(s):  
Richard J. Sohn ◽  
Aleksander A. Mathé ◽  
Crystal A. Leslie
Keyword(s):  
Cyclic Amp ◽  
Guinea Pig ◽  
Cyclic Gmp ◽  
Time Course

Rapid stimulation of Ins (1,4,5)P3 production in rat aorta by NE: correlation with contractile state

1993 ◽  
Vol 264 (1) ◽  
pp. H126-H132
Author(s):  
V. Pijuan ◽  
I. Sukholutskaya ◽  
W. G. Kerrick ◽  
M. Lam ◽  
C. van Breemen ◽  
...  
Keyword(s):  
Time Course ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Rat Aorta ◽  
Release Mechanism ◽  
Maximal Increase ◽  
Contractile State ◽  
Rapid Stimulation ◽  
Relationship Of ◽  
Stimulation Of

Rapid stimulation of Ins(1,4,5)P3 production in rat aorta by NE: correlation with contractile state. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H126-H132, 1993.--The isomeric composition of inositol phosphates generated in response to norepinephrine (NE) stimulation and the relationship of inositol phosphate production to release of intracellular Ca2+ as measured by contraction were characterized in rat aorta prelabeled with [3H]inositol. NE stimulated a rapid and transient increase in labeled D-myo-inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3] levels. A maximal increase in labeled Ins(1,4,5)P3 occurred within 15 s of stimulation followed by a decline to control levels at 5 min. D-Myo-inositol 1,3,4-trisphosphate [Ins-(1,3,4)P3] and D-myo-inositol 1-monophosphate [Ins(1)P] levels also increased rapidly in response to NE. In contrast to the transient production of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1)P production was maintained in the presence of NE. Half-maximal stimulation of Ins(1,4,5)P3 production and Ca2+ release occurred at 0.3 microM NE, and maximal effects were obtained with 10 microM NE. The concentration-response curve and time course for production of Ins(1,4,5)P3 correlated with the neurotransmitter-induced Ca2+ release from intracellular stores, indicating that the level of Ins(1,4,5)P3 regulated the Ca(2+)-release mechanism. In the continued presence of NE, the intracellular pools did not completely refill with Ca2+ despite the return of Ins-(1,4,5)P3 levels to basal at 5 min. These results demonstrate that NE stimulates a rapid increase in Ins(1,4,5)P3 that correlates with contraction in Ca(2+)-free buffer. The reuptake of Ca2+ into intracellular stores is regulated by a mechanism that may not involve Ins(1,4,5)P3.

DIFFERENTIAL STIMULATION OF INOSITOL TRISPHOSPHATE ACCUMULATION IN CULTURED HUMAN ENDOTHELIAL CELLS BY THROMBIN

1987 ◽  
Author(s):  
A J Carter ◽  
W G Eisert ◽  
T H Mμller
Keyword(s):  
Endothelial Cells ◽  
Time Course ◽  
Inositol Phosphate ◽  
Umbilical Vein ◽  
Inositol Trisphosphate ◽  
Specific Antigen ◽  
Enzymic Activity ◽  
Small Vessel ◽  
Human Endothelial Cells ◽  
Large Vessels

Vascular endothelial cells possess specific receptors for thrombin, and thrombin can interact with these receptors to activate the endothelial cells. However, the signal transduction mechanisms which mediate the cellular responses are not yet characterised. The aim of this study therefore, was to determine whether thrombin influenced the inositol phosphate transduction pathway in cultured human endothelial cells. Endothelial cells were isolated from both large and small vessels; these were human umbilical vein and the microvasculature of human omentum respectively. The endothelial cells stained positively with antibodies against Factor VIII antigen and another endothelial cell specific antigen (BMA 120). Pure human thrombin (0.1 - 10 units/ml) induced a dose-dependent formation of inositol phosphate, inositol biphosphate and inositol trisphosphate (IP3) in endothelial cells from large vessels prelabelled with tritiated inositol. The formation of IP3 was significantly increased after 15 sec., maximal after 1 min. and had returned almost to baseline levels after 4 min. This time course is consistent with its role as a second messenger. When the enzymic activity of thrombin was removed with phenylalanyl-prolyl-arginine chloromethyl ketone or d i i sopr opyIfluorophosphate, thrombin lost its ability to stimulate the accumulation of IP3. Thrombin at all concentrations tested was unable to stimulate the formation of IP3 in small vessel endothelial cells. However, IP3 formation could be stimulated by bradykinin (0.1-10 μM) in cells from both small and large vessels. The results demonstrate that active thrombin can induce the formation of IP3 in large vessel endothelium. But that there are differences in the way small vessel endothelium responds to thrombin.

Sign in / Sign up

Export Citation Format

Share Document