Relationship between secretagogue-induced Ca2+ release and inositol polyphosphate production in permeabilized pancreatic acinar cells.

Streb, Hanspeter; Heslop, John P.; Irvine, Robin F.; Schulz, Irene; Berridge, Michael P.

doi:10.1016/s0021-9258(17)39608-4

Cited by 169 publications

(8 citation statements)

References 38 publications

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“…The strongest separation between the two GTP-'y-S induced functions, amounting to a clear demonstration that they are mediated by distinct G-proteins, comes from the use of neomycin to block the PPI-pde activity (11,30). Neomycin is understood to prevent the action of PPI-pde by binding to the polar head groups of the PPIs (29).…”

Section: Discussionmentioning

confidence: 99%

“…In the experiments reported here we have used [3H]inositol-labeled mast cells permeabilized with streptolysin-O to follow the effects of Ca 2+ and guanosine 5"O-(3-thiotriphosphate) (GTP-T-S) on both PPI-pde activation Coy measurement of released [3H]inositol phosphates liPs]) and on secretion (release of histamine). We have used neomycin, an aminoglycoside antibiotic that is known to inhibit PPI-pde (11,30) to distinguish the effects of guanine nucleotides on PPI-pde activation and exocytosis. We find that guanosine 5'-O-(3-thiotfiphosphate) (GTP-y-S, a non-hydrolysable analogue of GTP) can still stimulate exocytosis under conditions where PPI-pde is fully inhibited by neomycin.…”

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confidence: 99%

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Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis.

Cockcroft

Howell

Gomperts

1987

The Journal of Cell Biology

196

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Abstract. Provision of GTP (or other nucleotidescapable of acting as ligands for activation of G-proteins) together with Ca 2+ (at micromolar concentrations) is both necessary and sufficient to stimulate exocytotic secretion from mast cells permeabilized with streptolysin-O. GTP and its analogues, through their interactions with Gp, also activate polyphosphoinositide-phosphodiesterase (PPI-pde generating inositol 1,4,5-trisphosphate and diglyceride [DG]). We have used mast cells labeled with [3H]inositol to test whether the requirement for GTP in exocytosis is an expression of Gp activity through the generation of DG and consequent activation of protein kinase C, or whether GTP is required at a later stage in the stimulus secretion sequence. Neomycin (0.3 mM) inhibits activation of PPI-pde, but maximal secretion due to optimal concentrations of guanosine 5"O-(3-thiotriphosphate) (GTP-'t-S) can still be evoked in its presence. When ATP is also provided the concentration requirement for GTP-u in support of exocytosis is reduced. This sparing effect of ATP is nullified when the PPI-pde reaction is inhibited by neomycin. We argue that the sparing effect of ATP occurs as a result of enhancement of DG production and through its action as a phosphoryl donor in the reactions catalyzed by protein kinase C. W,r~ have shown that rat mast ceils permeabilized with streptolysin-O undergo exocytotic secretion when provided with micromolar concentrations of Ca 2+ together with GTP, xanthosine triphosphate, or inosine triphosphate (18,19). These nucleotides are capable of acting as ligands for activation of G-proteins (5, 33). The combination of Ca 2+ + G~P is both necessary and sufficient for secretion to occur. There is no absolute requirement for the presence of any other water soluble metabolite though ATP has a sparing effect on the concentration requirements for both the Ca 2+ and the GTP. Since polyphosphoinositidephosphodiesterase (PPI-pde), t the enzyme that generates the second messengers inositol 1,4,5-trisphosphate and diglyceride (DG), is subject to control by a GTP-binding protein, Gp (9, 24, 26, 31), this represents one possible site of action whereby the effect of guanine nucleotides might act to control secretion in the permeabilized cells. It is now well understood that the water soluble product of PPI-txie activation, inositol 1,4,5-trisphosphate, mobilizes Ca 2+ from intracellular stores. DG is the activator of protein kinase C (4, 27). However, the existence of Gp, and a defined role for GTP in receptor activation mechanisms does not preclude 1. Abbreviations used in this paper: DG, diglyceride; GTP-y-S, guanosine 5'-O-(3-thiotriphosphate); IP, inositol phosphate; pale, phosphodiesterase; PIP, phosphatidylinositol monophosphate; PPI, polyphosphoinositide. the possibility that GTP might have other roles in the complete sequence of events which leads to exocytotic release of secretory materials.In the experiments reported here we have used [3H]inositol-labeled mast cells permeabilized with streptolysin-O to fo...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis.

Cockcroft

Howell

Gomperts

1987

The Journal of Cell Biology

196

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“…Figure 3 (A -D) show the inhibitory effects of various inhibitors on the lipolysis stimulation by the receptor antibody or leptin. H-89, a potent inhibitor of PKA (15); quin 2-AM, an intracellular Ca 2 ϩ chelator (16); W-7, a calmodulin antagonist (17); and neomycin, an inhibitor of phosphoinositide-specific phospholipase C (PLC) (18,19), all inhibited the stimulation of lipolysis by both the receptor antibody and leptin. These results suggest that the receptor antibody, as well as leptin, may stimulate the lipolysis via Ca 2 ϩ /calmodulin-and cAMP-dependent processes.…”

Section: Effects Of Various Inhibitors On the Stimulated Lipolysismentioning

confidence: 99%

Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads

Kawaji

Yoshida

Motoyashiki

et al. 2001

Journal of Lipid Research

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An anti-leptin receptor polyclonal antibody (receptor antibody), as well as leptin, stimulated the release of free fatty acids from isolated mouse fat pads in a timedependent manner. Following a 90-min incubation, maximal lipolysis was observed at 6 g/ml receptor antibody and 0.1 nM leptin. The receptor antibody did not show any additive effect to the stimulation of lipolysis induced by leptin, suggesting that they exert their actions through a similar mechanism involving the leptin receptor. N -[2-( pbromocinnamylamino) ethyl]-5-isoquinolinesulfonamide (H-89), quin 2-AM, N -(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and neomycin sulfate (neomycin) all potently inhibited the stimulation of lipolysis by the receptor antibody and leptin. Short-term incubation of the fat pads with the receptor antibody or leptin showed a transient increase in the cellular content of cAMP and myo -inositol 1,4,5-trisphosphate (IP 3 ) in similar concentrations to the free fatty acid release. Quin 2-AM and W-7 also inhibited the increase in cAMP content, suggesting that a Ca 2 ϩ /calmodulindependent process may be involved in a part of the mechanism in which the receptor antibody and leptin exert their effects. The increase in cellular IP 3 content via phosphoinositide-specific phospholipase C (PLC) sensitive to neomycin appears to be a primary step to initiate intracellular events. Both the receptor antibody and leptin may stimulate the lipolysis through mechanisms involving a transient increase in the cellular IP 3 content followed by cAMP production, which leads to the activation of cAMP-dependent protein kinase. -Kawaji, N., A. Yoshida, T. Motoyashiki, T. Morita, and H. Ueki. Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads.

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“…In particular, it has been suggested that Ins(1,4,5)P3, one of the products of PtdIns(4,5)P2 hydrolysis, is intimately involved in the rise in [Ca2+]i also seen upon occupation of these receptors. Briefly, the evidence is that Ins(1,4,5)P3 releases Ca2+ from an intracellular store, thought to be the endoplasmic reticulum [3][4][5][6], that InsP3 is rapidly accumulated in a Ca2+-independent manner after agonist binding [7,8], and that the same agonists promote rises of [Ca2+], in intact cells, which are at least initially independent of extracellular Ca2+ [9,10].…”

Section: Introductionmentioning

confidence: 99%

Rapid increases in inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and cytosolic free Ca2+ in agonist-stimulated pancreatic acini of the rat. Effect of carbachol, caerulein and secretin

Trimble¹,

Bruzzone²,

Meehan³

et al. 1987

Biochemical Journal

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We compared the time course of increases in isomers of inositol trisphosphate [Ins(1,4,5)P3] and Ins(1,3,4)P3] and the tetrakisphosphate [Ins(1,3,4,5)P4] with changes in cytosolic free Ca2+ [( Ca2+]i) in dispersed pancreatic acini of the rat. There were rapid (5s) increases in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 in response to carbachol, caerulein and secretin, whereas Ins(1,3,4)P3 increased more slowly. All three secretagogues induced increases in [Ca2+]i, which reached a peak at 15-20 s. Our results indicate that the very rapid formation of Ins(1,4,5)P3 is compatible with its second-messenger role in the initial elevation of [Ca2+]i.

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Relationship between secretagogue-induced Ca2+ release and inositol polyphosphate production in permeabilized pancreatic acinar cells.

Cited by 169 publications

References 38 publications

Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis.

Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis.

Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads

Rapid increases in inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and cytosolic free Ca2+ in agonist-stimulated pancreatic acini of the rat. Effect of carbachol, caerulein and secretin

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