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At least 955 records · Page 53Linked to original sources
PubMed1996

Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate. Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes.

Transient rise in nuclear calcium concentration is implicated in the regulation of events controlling gene expression. Mechanism by which calcium is transported to the nucleus is vehemently debated. Inositol 1,4,5-trisphosphate (InsP3) and inositol-1,3,4,5-tetrakisphosphate (InsP4) receptors have been located to the nucleus and their role in nuclear calcium signaling has been proposed. Outer nuclear membrane was separated from the inner membrane. The two membrane preparations were, as best as possible, devoid of cross contamination as attested by marker enzyme activity, Western blotting with antilamin antibody, and electron microscopy. InsP4 receptor and Ca(2+)-ATPase were located to the outer nuclear membrane. InsP3 receptor was located to the inner nuclear membrane. ATP or InsP4 induced nuclear calcium uptake. External free calcium concentration, in the medium bathing the nuclei, determined the choice for ATP or InsP4-mediated calcium transport. We present a mechanistic model for nuclear calcium transport. According to this model, calcium can reach the nucleus envelope either by the action of ATP or InsP4. However, the calcium release from the nucleus envelope to the nucleoplasm is mediated by InsP3 through the activation of InsP3 receptor, which is located to the inner nuclear membrane. The action of InsP3 in this process was instantaneous and transient and was sensitive to heparin.

Adenosine Triphosphate↗
PubMed1989

Differences in the adenosine receptors modulating inositol phosphates and cyclic AMP accumulation in mammalian cerebral cortex.

1. 2-Chloroadenosine stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation and potentiated (guinea-pig) or inhibited (mouse) the histamine H1-receptor-stimulated hydrolysis of inositol phospholipids in slices of guinea-pig and mouse cerebral cortex. 2. Two xanthine-based adenosine receptor antagonists were identified which were one order of magnitude more potent at the adenosine receptor mediating augmentation of the histamine-stimulated inositol phospholipid hydrolysis than at the receptor linked to cyclic AMP formation in guinea-pig cerebral cortical slices. 3. These compounds, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 7-benzyl-3-(2-methylpropyl)xanthine (BMPX) retained their selectivity under near-identical incubation conditions in both assays. 4. These compounds also showed similar affinities and selectivity for the adenosine receptor mediating inhibition of histamine-stimulated inositol phospholipid hydrolysis in mouse cerebral cortical slices. 5. Inclusion of agents which give rise to, or mimic, high levels of cyclic AMP (forskolin (1 microM), 8-bromo-cyclic AMP (1 mM) and vasoactive intestinal polypeptide (1 microM] in the incubation medium failed to mimic the action of 2-chloroadenosine on inositol phospholipid turnover in cerebral cortical slices from either species. 6. These data suggest that the adenosine receptor modulating the hydrolysis of inositol phospholipid in mouse and guinea-pig cerebral cortical slices is different from the adenosine receptor linked to cyclic AMP formation, and, furthermore, that the modulation of inositol phospholipid metabolism in either species is not mediated via alterations in cyclic AMP levels.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Exposure to the n-3 polyunsaturated fatty acid docosahexaenoic acid impairs alpha 1-adrenoceptor-mediated contractile responses and inositol phosphate formation in rat cardiomyocytes.

The beneficial effects of n-3 polyunsaturated fatty acids of fish oil in the prevention of fatal arrhythmias in myocardial ischemia were suggested to be at least in part mediated by a modulation of dihydropyridine-sensitive L-type calcium channels. As cardiac alpha 1-adrenoceptor stimulation has been suggested to have no significant effect on L-type calcium channels, the aim of this study using cultured neonatal rat cardiomyocytes was to investigate whether chronic n-3 polyunsaturated fatty acid exposure may have an influence on alpha 1-adrenoceptor-induced positive inotropic effects and induction of arrhythmias. Pretreatment of the rat cardiomyocytes for 3 days in the presence of the n-3 polyunsaturated fish oil-derived fatty acid docosahexaenoic acid (60 mumol/l) markedly decreased alpha 1-adrenoceptor-stimulated increase in contraction velocity and induction of arrhythmias. The increase in contraction velocity of the cardiomyocytes induced by the beta-adrenoceptor agonist isoprenaline was also markedly reduced by the n-3 fatty acid pretreatment. Basal contractile amplitude and spontaneous beating frequency of the cardiomyocytes were not significantly altered by the docosahexaenoic acid exposure. The pretreatment of the rat cardiomyocytes for 3 days in the presence of docosahexaenoic acid (60 mumol/l) decreased alpha 1-adrenoceptor-stimulated formation of the calcium-mobilizing second messenger IP3 and its metabolites IP2 and IP1 by 55%. The depression of IP3 formation by docosahexaenoic acid treatment was not mediated by a decreased uptake of myo-inositol into the cardiomyocytes nor by a decreased synthesis of phosphatidylinositol bisphosphate (PIP2), the substrate of phospholipase C. The level of glycerol-3-phosphate, an important substrate of the phosphoinositide cycle, was unaltered by the docosahexaenoic acid pretreatment. Receptor binding studies revealed that the dissociation constant and maximal binding capacity of the alpha 1-adrenoceptor antagonist (3H)prazosin was unchanged by the n-3 polyunsaturated fatty acid exposure. Beta-Adrenoceptor-and forskolin-stimulated adenylyl cyclase activities were not diminished by the docosahexaenoic acid pretreatment. Chronic exposure of the cardiomyocytes to the n-6 polyunsaturated fatty acid arachidonic acid (60 mumol/l) did neither significantly alter alpha 1-adrenoceptor-induced inositol phosphate formation nor alpha 1-adrenoceptor-stimulated increase in contraction velocity. The results presented show that chronic n-3 polyunsaturated fatty acid pretreatment of rat cardiomyocytes leads to a marked impairment of alpha 1-adrenoceptor-induced positive inotropic effects and induction of arrhythmias concomitant with a n-3 fatty acid-induced decrease in IP3 formation. This derangement of the phosphoinositide pathway by chronic n-3 fatty acid exposure may, thus, contribute to the beneficial effects of fish oil-derived fatty acids in the prevention of fatal arrhythmias in myocardial ischemia.

Adenylyl Cyclases↗
PubMed1986

Inositol phosphate production following alpha 1-adrenergic, muscarinic or electrical stimulation in isolated rat heart.

A possible participation of polyphosphoinositide metabolism in the excitation-contraction coupling in heart was investigated. Isolated rat ventricles prelabelled with myo-[2-3H]inositol were stimulated by conditions that increase mechanical activity. Both noradrenaline and carbachol increased the basal level of IP3, IP2 and IP by the activation of alpha 1-adrenergic and muscarinic receptors, respectively. Electrical stimulation accelerated inositol lipid degradation by phospholipase C thus enhancing the IP3 level as compared to quiescent ventricles. It is proposed that IP3 may be involved in excitation-contraction coupling in cardiac tissue.

Animals↗