Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid mobilization of Ca2+ from internal stores of both cell types. Paradoxically, alpha 1-adrenergic agonists did not rapidly increase inositol trisphosphate (Ins-P3) formation in BC3H-1 cells, in distinction to the rapid increase in Ins-P3 accumulation observed in 1321N1 cells after muscarinic stimulation. To determine whether the variations observed in the Ins-P3 response could be ascribed to differences in the relative amounts of inositol 1,4,5-trisphosphate, inositol 1,3,4-trisphosphate, and inositol tetrakisphosphate (respectively, Ins-1,4,5-P3, Ins-1,3,4-P3, and Ins-P4), we have separated the individual inositol phosphates by high-performance liquid chromatography and examined the rates of conversion of individual inositol phosphates in the two types of cells. Muscarinic stimulation of 1321N1 cells resulted in increased Ins-1,4,5-P3 production, as well as the rapid production of Ins-1,3,4-P3 and Ins-P4. Application of alpha 1-agonist to BC3H-1 cells produced a modest but delayed increase in accumulation of Ins-1,4,5-P3. Adrenergic stimulation also resulted in a smaller and even slower production of Ins-1,3,4-P3, and Ins-P4 could not be detected in BC3H-1 cells under any conditions employed. Thus, over a 30-sec interval in which Ca2+ is mobilized to a maximum extent, increases in Ins-1,4,5-P3, Ins-1,3,4-P3, or Ins-P4 amounted to less than 10% over basal values in BC3H-1 cells. These results indicate that the regulation of Ins-P3 isomer formation and conversion may vary substantially between different cell types. In addition, if inositol 1,4,5-trisphosphate is the sole mediator of intracellular Ca2+ release, it is necessary to propose that an increase in Ins-1,4,5-P3 sufficient to mobilize Ca2+ rapidly may occur only within discrete cellular localities in some cell types. According, it may not be possible to detect the increases in Ins-1,4,5-P3 over basal concentrations when measuring total cellular inositol phosphates.
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PMID:Receptor-mediated inositol phosphate formation in relation to calcium mobilization: a comparison of two cell lines. 282 90

Although activation of muscarinic cholinergic receptors on 1321N1 human astrocytoma cells results in a linear accumulation of inositol phosphates for up to 60 min in the presence of LiCl [Masters, Quinn & Brown (1985) Mol. Pharmacol. 27, 325-332], activation of H1-histamine receptors resulted in an increase in total inositol phosphate formation that was maintained for less than 5 min. The effects of stimulation of these two receptors on accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] were also examined. Incubation of 1321N1 cells with carbachol resulted in a rapid accumulation of all three inositol phosphates, reaching a maximum within 30 s; this elevated value was maintained for up to 60 min. The rate of disappearance of Ins(1,3,4)P3 from carbachol-treated cells after the addition of atropine paralleled or exceeded the rate of disappearance of Ins(1,4,5)P3. Although the initial rates of accumulation of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1,3,4,5)P4 in the presence of histamine were similar to that observed with carbachol, the amounts of these inositol phosphates had returned to control values within 5 min after the addition of histamine. The results indicate that, although the acute effects of muscarinic receptor and H1-histamine receptor stimulation on phosphoinositide hydrolysis are very similar, the histamine receptor is desensitized rapidly, whereas the muscarinic receptor is not. This effect on histamine-receptor function is apparently homologous, since preincubation of 1321N1 cells with histamine did not decrease the subsequent response to carbachol.
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PMID:Regulation of inositol trisphosphate accumulation by muscarinic cholinergic and H1-histamine receptors on human astrocytoma cells. Differential induction of desensitization by agonists. 359 97

1. An inositol trisphosphate (InsP3) distinct from Ins(1,4,5)P3 and Ins(1,3,4)P3, which we previously observed in myeloid and lymphoid cells [French, Bunce, Stephens, Lord, McConnell, Brown, Creba and Michell (1991) Proc R. Soc. London B 245, 193-201; Bunce, French, Allen, Mountford, Moore, Greaves, Michell and Brown (1993) Biochem. J. 289, 667-673], is present in WRK1 rat mammary tumour cells and pancreatic endocrine beta-cells. 2. It has been identified as Ins(1,2,3)P3 by a combination of oxidation to ribitol, a structurally diagnostic polyol, and ammoniacal hydrolysis to identified inositol monophosphates. 3. Ins(1,2,3)P3 concentration in HL60 cells changed little during stimulation by ATP or fMetLeuPhe or during neutrophilic or monocytic differentiation, and Ins(1,2,3)P3 was unresponsive to vasopressin in WRK1 cells. 4. Ins(1,2,3)P3 was usually more abundant than Ins(1,4,5)P3, often being present at concentrations between approximately 1 microM and approximately 10 microM. 5. HL60, WRK-1 and lymphoid cells also contain Ins(1,2)P2 or Ins(2,3)P2, or a mixture of these two enantiomers, as a major InsP2 species. 6. Ins(1,2,3)P3 and Ins(1,2)P2/Ins(2,3)P2 are readily detected in cells labelled for long periods, but not in acutely labelled cells. This behaviour resembles that of InsP6, the most abundant cellular inositol polyphosphate that includes the 1,2,3-trisphosphate motif, which also achieves isotopic equilibrium with inositol only slowly. 7. Ins(1,2,3)P3 is the major InsP3 that accumulates during metabolism of InsP6 by WRK-1 cell homogenates. 8. Possible metabolic relationships between Ins(1,2,3)P3, Ins(1,2)P2/Ins(2,3)P2 and other inositol polyphosphates in cells, and a possible role for Ins(1,2,3)P3 in cellular iron handling, are considered.
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PMID:Inositol 1,2,3-trisphosphate and inositol 1,2- and/or 2,3-bisphosphate are normal constituents of mammalian cells. 788 11