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Biomedical subjects

R F Irvine

Publications and source records attributed to R F Irvine.

180 records · Page 10Linked to original sources
PubMed1977

Phosphatidylinositol-degrading enzymes in liver lysosomes.

The major pathway by which liver lysosomal enzymes degrade phosphatidylinositol is through an EDTA-insensitive formation of phosphorylinositol. This is in distinct contrast with the Ca2+-dependent production of phosphorylinositol from phosphatidylinositol, which is located in the cytosol. Lysosomal enzymes can also totally deacylate phosphatidylinositol, producing glycerophosphorylinositol.

Acid Phosphatase↗
PubMed1973

The effect of ethylene on (1-14C)glycerol incorporation into phospholipids of etiolated pea stems.

The effect of ethylene (10 p.p.m.) on the rate of incorporation of [1-(14)C]glycerol into phospholipids of etiolated pea stems was studied. After 2-3h treatment with ethylene, incorporation was decreased by 50%. It remained at this value for as long as ethylene was supplied (8h). Handling the plants also caused a temporary decrease in incorporation, which we attribute to the production of endogenous ;wound' ethylene. The percentage decrease in incorporation was the same in four major phospholipid fractions, i.e. phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol.

Carbon Radioisotopes↗
PubMedDate not supplied

Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate.

Activation of receptors for a wide variety of hormones and neurotransmitters leads to an increase in the intracellular level of calcium. Much of this calcium is released from intracellular stores but the link between surface receptors and this internal calcium reservoir is unknown. Hydrolysis of the phosphoinositides, which is another characteristic feature of these receptors, has been implicated in calcium mobilization. The primary lipid substrates for the receptor mechanism seem to be two polyphosphoinositides, phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2), which are rapidly hydrolysed following receptor activation in various cells and tissues. The action of phospholipase C on these polyphosphoinositides results in the rapid formation of the water-soluble products inositol 1,4-bisphosphate (Ins1,4P2) and inositol 1,4,5-trisphosphate (Ins1,4,5P3). In the insect salivary gland, where changes in Ins1,4P2 and Ins1,4,5P2 have been studied at early time periods, increases in these inositol phosphates are sufficiently rapid to suggest that they might mobilize internal calcium. We report here that micromolar concentrations of Ins1,4,5P3 release Ca2+ from a nonmitochondrial intracellular Ca2+ store in pancreatic acinar cells. Our results strongly suggest that this is the same Ca2+ store that is released by acetylcholine.

Adenosine Triphosphate↗
PubMedDate not supplied

The second messenger linking receptor activation to internal Ca release in liver.

The increase in cytosolic [Ca2+] induced by Ca-mobilizing hormones in liver is mainly due to release of Ca from intracellular stores. For Ca to be released from internal sites a messenger must be formed at the plasma membrane which diffuses into the cytosol to signal Ca release from the intracellular organelles. One of the first actions of these hormones is to cause breakdown of the polyphosphoinositides to form soluble inositol phosphates. Some evidence for the idea that these substances could be the second messenger has been obtained in pancreatic acinar cells. Here we have found that hormone activation of hepatocytes causes rapid breakdown of phosphatidylinositol 4,5-bisphosphate [ PtdIns (4,5)P2] to form inositol trisphosphate ( InsP3 ). When applied to permeabilized hepatocytes, InsP3 releases Ca from non-mitochondrial ATP-dependent pools. This suggests that InsP3 could be the messenger linking Ca-mobilizing receptor activation to intracellular Ca release in liver.

Animals↗
PubMedDate not supplied

Rapid mobilization of Ca2+ from rat insulinoma microsomes by inositol-1,4,5-trisphosphate.

Several hormones and neurotransmitters raise the cytosolic free Ca2+ concentration by stimulating the influx of Ca2+ and/or by mobilizing stored Ca2+. However, the link between the agonist receptor on the cell surface and the organelle(s) from which Ca2+ is mobilized is unknown. One feature of the agonists that increase cytosolic Ca2+ is their rapid induction of phosphatidylinositol turnover and polyphosphoinositide hydrolysis; in some tissues this leads, within seconds, to a marked accumulation of the water-soluble products, inositol 1,4-bisphosphate ( Ins1 , 4P2 ) and inositol-1,4,5- trisphosphate ( Ins1 ,4, 5P3 ), suggesting that these might mediate Ca2+ mobilization from internal pools. Such an action of Ins1 ,4, 5P3 has recently been inferred from studies with permeabilized pancreatic acinar cells and hepatocytes. Here we show directly that Ins1 ,4, 5P3 rapidly releases Ca2+ from a microsomal fraction of rat insulinoma but not from mitochondria or secretory granules. Moreover, this response is transient and desensitizes the microsomes to subsequent Ins1 ,4, 5P3 additions. These results suggest that Ins1 ,4, 5P3 functions as a cellular messenger inducing early mobilization of Ca2+ from the endoplasmic reticulum.

Adenoma, Islet Cell↗
PubMedDate not supplied

Photoreceptor excitation and adaptation by inositol 1,4,5-trisphosphate.

A central question concerning vision is the identity of the biochemical pathway that underlies phototransduction. The large size of the ventral photoreceptors of Limulus polyphemus renders them a favourite preparation for investigating this problem. The fact that a single photon opens approximately 1,000 ionic channels in these photoreceptors suggests the need for an internal transmitter. We have investigated whether inositol 1,4,5-trisphosphate (InsP3) functions as such an internal transmitter, given that InsP3 may act as an intracellular messenger in other cellular processes. Here we report that in Limulus, intracellular pressure injection of InsP3 both excites and adapts ventral photoreceptors in a manner similar to light.

Action Potentials↗
PubMedDate not supplied

myo-Inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors.

Photoreceptor excitation begins with the absorption of a photon by rhodopsin and proceeds through an unknown sequence of steps that leads to changes in specific ionic conductances. These conductance changes produce the receptor potential. It has been proposed that hydrolysis of phosphoinositides is involved in the control of a variety of physiological processes. Recent studies have implicated inositol 1,4,5-trisphosphate as an intracellular messenger in the cascade mediating hormone-stimulated secretion. We propose that one of the steps in the excitatory cascade in Limulus ventral photoreceptors may be an increase in intracellular concentration of myo-inositol polyphosphates, derived from hydrolysis of the membrane component phosphatidylinositol bisphosphate by a phospholipase. Here we present biochemical and electrophysiological evidence that an inositol polyphosphate may be an intracellular messenger in the cascade mediating excitation, based on the following criteria: the cells possess the synthetic and degradative metabolism for the messenger; the natural stimulus leads to a change in the concentration of the messenger within the cells; and intracellular injection of exogenous messenger mimics naturally occurring electrophysiological events.

Animals↗
PubMedDate not supplied

Inositol trisphosphate, a novel second messenger in cellular signal transduction.

There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

Animals↗
PubMedDate not supplied

The inositol tris/tetrakisphosphate pathway--demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues.

Recent advances in our understanding of the role of inositides in cell signalling have led to the central hypothesis that a receptor-stimulated phosphodiesteratic hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) results in the formation of two second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). The existence of another pathway of inositide metabolism was first suggested by the discovery that a novel inositol trisphosphate, Ins(1,3,4)P3, is formed in stimulated tissues; the metabolic kinetics of Ins(1,3,4)P3 are entirely different from those of Ins(1,4,5)P3 (refs 6, 7). The probable route of formation of Ins(1,3,4)P3 was recently shown to be via a 5-dephosphorylation of inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), a compound which is rapidly formed on muscarinic stimulation of brain slices, and which can be readily converted to Ins(1,3,4)P3 by a 5-phosphatase in red blood cell membranes. However, the source of Ins(1,3,4,5)P4 is unclear, and an attempt to detect a possible parent lipid, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), was unsuccessful. The recent discovery that the higher phosphorylated forms of inositol (InsP5 and InsP6) also exist in animal cells suggested that inositol phosphate kinases might not be confined to plant and avian tissues, and here we show that a variety of animal tissues contain an active and specific Ins(1,4,5)P3 3-kinase. We therefore suggest that an inositol tris/tetrakisphosphate pathway exists as an alternative route to the dephosphorylation of Ins(1,4,5)P3. The function of this novel pathway is unknown.

Animals↗
PubMedDate not supplied

Synergism of inositol trisphosphate and tetrakisphosphate in activating Ca2+-dependent K+ channels.

Inositol 1,4,5-trisphosphate (Ins P3) is a second messenger releasing intracellular Ca2+ into the cytosol. It has recently been proposed that inositol 1,3,4,5-tetrakisphosphate (Ins P4), which is formed from Ins P3 by Ins P3-3-kinase, acts with Ins P3 as a second messenger by promoting extracellular Ca2+ entry. It has been suggested that Ins P3 itself can act to stimulate Ca2+ uptake from the extracellular fluid, although a physiological function for Ins P4 was not excluded. Transmembrane currents can now be measured in single cells by voltage clamping under conditions where the intracellular perfusion fluid can be changed several times during individual experiments. We have used this method to test the effects of Ins P3 and Ins P4 on the Ca2+-activated K+ current, and now show that neither Ins P3 alone nor Ins P4 alone can activate a sustained current, whereas Ins P3 and Ins P4 in combination evoke a sustained increase in Ca2+-activated K+ current which is dependent on external Ca2+.

Animals↗