Rapid activation and partial inactivation of inositol trisphosphate receptors by adenophostin A

Adenophostin A, the most potent known agonist of inositol 1,4,5-trisphosphate (InsP3) receptors, stimulated 45Ca2+ release from the intracellular stores of permeabilized hepatocytes. The concentration of adenophostin A causing the half-maximal effect (EC50) was 7.1±0.5nM, whereas the EC50 for InsP3 was 177±26nM; both responses were positively co-operative. In rapid superfusion analyses of 45Ca2+ release from the intracellular stores of immobilized hepatocytes, maximal concentrations of adenophostin A or InsP3 evoked indistinguishable patterns of Ca2+ release. The Ca2+ release evoked by both agonists peaked at the same maximal rate after about 375ms and the activity of the receptors then decayed to a stable, partially (60%) inactivated state with a half-time (t1/2) of 318±29ms for adenophostin A and 321±22ms for InsP3. Dissociation rates were measured by recording rates of InsP3-receptor channel closure after rapid removal of agonist. The rate of adenophostin A dissociation (t1/2, 840±195ms) was only 2-fold slower than that of InsP3 (t1/2, 436±48ms). We conclude that slow dissociation of adenophostin A from InsP3 receptors does not underlie either its high-affinity binding or the reported differences in the Ca2+ signals evoked by InsP3 and adenophostin A in intact cells.

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Rapid activation and partial inactivation of inositol trisphosphate receptors by adenophostin A

Biochemical Journal ◽

10.1042/0264-6021:3520929 ◽

2000 ◽

Vol 352 (3) ◽

pp. 929 ◽

Cited By ~ 9

Author(s):

Charles E. ADKINS ◽

Frank WISSING ◽

Barry V.L. POTTER ◽

Colin W. TAYLOR

Keyword(s):

Inositol Trisphosphate ◽

Inositol Trisphosphate Receptors ◽

Adenophostin A ◽

Partial Inactivation ◽

Rapid Activation

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Effects of Ca2+ chelators on purified inositol 1,4,5-trisphosphate (InsP3) receptors and InsP3-stimulated Ca2+ mobilization

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)50232-0 ◽

1993 ◽

Vol 268 (16) ◽

pp. 11528-11533

Author(s):

A. Richardson ◽

C.W. Taylor

Keyword(s):

Inositol 1,4,5 Trisphosphate ◽

Insp3 Receptors

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Inframolecular Studies of the Protonation of Adenophostin A: Comparison with 1-d-myo-Inositol 1,4,5-Trisphosphate

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1999.1832 ◽

1999 ◽

Vol 266 (2) ◽

pp. 334-340 ◽

Cited By ~ 11

Author(s):

Marc Felemez ◽

Rachel D. Marwood ◽

Barry V.L. Potter ◽

Bernard Spiess

Keyword(s):

Inositol 1,4,5 Trisphosphate ◽

Adenophostin A

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Characterization of the inositol 1,4,5-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate

Biochemical Journal ◽

10.1042/bj2620083 ◽

1989 ◽

Vol 262 (1) ◽

pp. 83-89 ◽

Cited By ~ 48

Author(s):

K J Föhr ◽

J Scott ◽

G Ahnert-Hilger ◽

M Gratzl

Keyword(s):

Endocrine Cells ◽

Calcium Release ◽

Cell Types ◽

Inhibitory Effect ◽

Maximal Effect ◽

Thiol Compounds ◽

Inositol 1,4,5 Trisphosphate ◽

Dependent Inhibition ◽

Pheochromocytoma Pc12 ◽

First Time

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.

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Caffeine-induced inhibition of inositol(1,4,5)-trisphosphate-gated calcium channels from cerebellum.

Molecular Biology of the Cell ◽

10.1091/mbc.5.1.97 ◽

1994 ◽

Vol 5 (1) ◽

pp. 97-103 ◽

Cited By ~ 57

Author(s):

I Bezprozvanny ◽

S Bezprozvannaya ◽

B E Ehrlich

Keyword(s):

Lipid Bilayers ◽

Inhibitory Action ◽

Single Channel ◽

Ryanodine Receptors ◽

Single Channels ◽

Ca Channels ◽

Open Time ◽

Inositol 1,4,5 Trisphosphate ◽

Insp3 Receptors ◽

Intracellular Ca

Effects of the xanthine drug caffeine on inositol (1,4,5)-trisphosphate (InsP3)-gated calcium (Ca) channels from canine cerebellum were studied using single channels incorporated into planar lipid bilayers. Caffeine, used widely as an agonist of ryanodine receptors, inhibited the activity of InsP3-gated Ca channels in a noncooperative fashion with half-inhibition at 1.64 mM caffeine. The frequency of channel openings was decreased more than threefold after addition of 5 mM caffeine; there was only a small effect on mean open time of the channels, and the single channel conductance was unchanged. Increased InsP3 concentration overcame the inhibitory action of caffeine, but caffeine did not reduce specific [3H]InsP3 binding to the receptor. The inhibitory action of caffeine on InsP3 receptors suggests that the action of caffeine on the intracellular Ca pool must be interpreted with caution when both ryanodine receptors and InsP3 receptors are present in the cell.

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Adenophostin A Can Stimulate Ca2+Influx without Depleting the Inositol 1,4,5-Trisphosphate-sensitive Ca2+Stores in theXenopusOocyte

Journal of Biological Chemistry ◽

10.1074/jbc.272.15.9956 ◽

1997 ◽

Vol 272 (15) ◽

pp. 9956-9961 ◽

Cited By ~ 22

Author(s):

Sylvain DeLisle ◽

Erik W. Marksberry ◽

Carl Bonnett ◽

David J. Jenkins ◽

Barry V. L. Potter ◽

...

Keyword(s):

Inositol 1,4,5 Trisphosphate ◽

Adenophostin A

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The temporal relationship between phospholipase activation, diradylglycerol formation and superoxide production in the human neutrophil

Biochemical Journal ◽

10.1042/bj2710209 ◽

1990 ◽

Vol 271 (1) ◽

pp. 209-213 ◽

Cited By ~ 30

Author(s):

N T Thompson ◽

J E Tateson ◽

R W Randall ◽

G D Spacey ◽

R W Bonser ◽

...

Keyword(s):

Phospholipase D ◽

Human Neutrophil ◽

Second Messengers ◽

Superoxide Production ◽

Human Neutrophils ◽

Inositol 1,4,5 Trisphosphate ◽

Phosphatidate Phosphohydrolase ◽

Time Courses ◽

Rapid Activation ◽

Stimulation Of

Fluctuations in the amounts of choline, inositol 1,4,5-trisphosphate (IP3) and diradylglycerol have been used to monitor phospholipase activation in the human neutrophil. Stimulation of human neutrophils by formylmethionyl-leucylphenylalanine (fMet-Leu-Phe) resulted in a rapid activation of both phosphatidylinositol 4,5-bisphosphate breakdown by phospholipase C and phosphatidylcholine breakdown by phospholipase D. Diradylglycerol accumulation occurred more slowly than that of either choline or IP3 and was inhibited by 30 mM-butanol, suggesting that the bulk was derived from the phospholipase D pathway via phosphatidate phosphohydrolase. Consistent with this is the observation that choline and diradylglycerol are produced in similar amounts. 1,2-Diacylglycerol (DAG) and 1-O-alkyl-2-acyl-sn-glycerol species accumulated with different time courses, indicating that one or more steps in the phospholipase D pathway was selective for the diacyl species. Superoxide production by fMet-Leu-Phe-stimulated neutrophils paralleled DAG accumulation over the first 5 min, but thereafter this production stopped, despite the fact that DAG remained elevated. We conclude that DAG derived from the phospholipase D pathway is only one of the second messengers important in controlling this functional response.

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Adenine-nucleotide binding sites on the inositol 1,4,5-trisphosphate receptor bind caffeine, but not adenophostin A or cyclic ADP-ribose

Cell Calcium ◽

10.1054/ceca.1998.0011 ◽

1999 ◽

Vol 25 (2) ◽

pp. 143-152 ◽

Cited By ~ 33

Author(s):

K. Maes ◽

L. Missiaen ◽

J.B. Parys ◽

I. Sienaert ◽

G. Bultynck ◽

...

Keyword(s):

Binding Sites ◽

Adenine Nucleotide ◽

Nucleotide Binding ◽

Nucleotide Binding Sites ◽

Cyclic Adp Ribose ◽

Inositol 1,4,5 Trisphosphate ◽

Adenophostin A ◽

Trisphosphate Receptor

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Mechanism of phorbol ester inhibition of histamine-induced IP3 formation in cultured airway smooth muscle

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1989.257.4.l209 ◽

1989 ◽

Vol 257 (4) ◽

pp. L209-L216 ◽

Cited By ~ 2

Author(s):

R. K. Murray ◽

C. F. Bennett ◽

S. J. Fluharty ◽

M. I. Kotlikoff

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Calcium Release ◽

Calcium Sensitivity ◽

Cytosolic Calcium ◽

Guanine Nucleotide ◽

Intact Cells ◽

Kinase C ◽

Inositol 1,4,5 Trisphosphate ◽

Site Of Action

Cytosolic calcium is a key determinant of the contractile state of airway smooth muscle (ASM). To investigate the mechanisms by which histamine affects cytosolic calcium, we measured changes in inositol 1,4,5-trisphosphate (IP3) following the addition of histamine to cultured canine ASM cells. The effect of phorbol 12-myristate 13-acetate (PMA) on IP3 formation was investigated under conditions previously shown to abolish histamine-induced calcium release. In both intact cells and ASM membranes, histamine produced a significant increase in IP3 formation, which was inhibited by PMA. The site of this blockade was investigated by examining the effect of PMA on guanine nucleotide-stimulated IP3 formation and on phosphoinositide-specific phospholipase C (PI-PLC) activity in ASM membranes. Guanine nucleotide-stimulated IP3 formation was inhibited by PMA pretreatment. Membrane-associated PI-PLC activity was also decreased, an effect that was not due simply to a shift in the calcium sensitivity of the enzyme. We conclude that in cultured canine ASM cells, PMA blocks histamine-induced IP3 formation and that this inhibition is caused, in part, by a postreceptor site of action of protein kinase C, possibly via a direct effect on PI-PLC.

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