Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate

In the rat pancreatoma cell line, AR4-2J, three inositol tetrakisphosphate isomers were identified, (1,3,4,6), (1,3,4,5), (3,4,5,6), which were increased during activation of phospholipase C by bombesin. Two other isomers were identified, (1,4,5,6) and a fifth isomer which was either (1,2,3,4) or (1...

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Veröffentlicht in:The Journal of biological chemistry 1990-07, Vol.265 (19), p.11167-11176
Hauptverfasser: F S Menniti, K G Oliver, K Nogimori, J F Obie, S B Shears, J W Putney, Jr
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container_issue 19
container_start_page 11167
container_title The Journal of biological chemistry
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creator F S Menniti
K G Oliver
K Nogimori
J F Obie
S B Shears
J W Putney, Jr
description In the rat pancreatoma cell line, AR4-2J, three inositol tetrakisphosphate isomers were identified, (1,3,4,6), (1,3,4,5), (3,4,5,6), which were increased during activation of phospholipase C by bombesin. Two other isomers were identified, (1,4,5,6) and a fifth isomer which was either (1,2,3,4) or (1,2,3,6), which have not previously been detected in any cell type. To study the metabolic interrelationships between these compounds and inositol 1,3,4,5,6-pentakisphosphate in the intact cell, their turnover was assessed under different protocols of [3H]myo-inositol labeling; the inositol phosphates were labeled to near steady state or under conditions where either rapidly or slowly turning over inositol polyphosphates were preferentially labeled. The relative specific radioactivities of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, inositol 1,3,4-trisphosphate, and inositol 1,3,4,6-tetrakisphosphate were very similar in bombesin-stimulated cells, consistent with the pathway for the conversion of inositol 1,4,5-trisphosphate to the other three inositol polyphosphates. Compared with these inositol phosphates, the turnover of inositol 1,3,4,5,6-pentakisphosphate was slow. An accumulation of radioactivity into inositol 1,3,4,5,6-pentakisphosphate was observed only under labeling conditions where its relative specific radioactivity was substantially below that of inositol 1,3,4,6-tetrakisphosphate. This indicated that the precursor for de novo synthesis of inositol 1,3,4,5,6-pentakisphosphate was inositol 1,3,4,6-tetrakisphosphate. Bombesin stimulated the net breakdown of inositol 1,3,4,5,6-pentakisphosphate and increased the level of inositol 3,4,5,6-tetrakisphosphate; the relative specific radioactivities of these two compounds were similar under all conditions. These data led to the novel proposal that inositol 3,4,5,6-tetrakisphosphate is the product of inositol 1,3,4,5,6-pentakisphosphate breakdown. This reaction was apparently stimulated by a regulated change in the enzyme(s) which interconvert inositol 1,3,4,5,6-pentakisphosphate and inositol 3,4,5,6-tetrakisphosphate.
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To study the metabolic interrelationships between these compounds and inositol 1,3,4,5,6-pentakisphosphate in the intact cell, their turnover was assessed under different protocols of [3H]myo-inositol labeling; the inositol phosphates were labeled to near steady state or under conditions where either rapidly or slowly turning over inositol polyphosphates were preferentially labeled. The relative specific radioactivities of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, inositol 1,3,4-trisphosphate, and inositol 1,3,4,6-tetrakisphosphate were very similar in bombesin-stimulated cells, consistent with the pathway for the conversion of inositol 1,4,5-trisphosphate to the other three inositol polyphosphates. Compared with these inositol phosphates, the turnover of inositol 1,3,4,5,6-pentakisphosphate was slow. An accumulation of radioactivity into inositol 1,3,4,5,6-pentakisphosphate was observed only under labeling conditions where its relative specific radioactivity was substantially below that of inositol 1,3,4,6-tetrakisphosphate. This indicated that the precursor for de novo synthesis of inositol 1,3,4,5,6-pentakisphosphate was inositol 1,3,4,6-tetrakisphosphate. Bombesin stimulated the net breakdown of inositol 1,3,4,5,6-pentakisphosphate and increased the level of inositol 3,4,5,6-tetrakisphosphate; the relative specific radioactivities of these two compounds were similar under all conditions. These data led to the novel proposal that inositol 3,4,5,6-tetrakisphosphate is the product of inositol 1,3,4,5,6-pentakisphosphate breakdown. 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Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>In the rat pancreatoma cell line, AR4-2J, three inositol tetrakisphosphate isomers were identified, (1,3,4,6), (1,3,4,5), (3,4,5,6), which were increased during activation of phospholipase C by bombesin. Two other isomers were identified, (1,4,5,6) and a fifth isomer which was either (1,2,3,4) or (1,2,3,6), which have not previously been detected in any cell type. To study the metabolic interrelationships between these compounds and inositol 1,3,4,5,6-pentakisphosphate in the intact cell, their turnover was assessed under different protocols of [3H]myo-inositol labeling; the inositol phosphates were labeled to near steady state or under conditions where either rapidly or slowly turning over inositol polyphosphates were preferentially labeled. The relative specific radioactivities of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, inositol 1,3,4-trisphosphate, and inositol 1,3,4,6-tetrakisphosphate were very similar in bombesin-stimulated cells, consistent with the pathway for the conversion of inositol 1,4,5-trisphosphate to the other three inositol polyphosphates. Compared with these inositol phosphates, the turnover of inositol 1,3,4,5,6-pentakisphosphate was slow. An accumulation of radioactivity into inositol 1,3,4,5,6-pentakisphosphate was observed only under labeling conditions where its relative specific radioactivity was substantially below that of inositol 1,3,4,6-tetrakisphosphate. This indicated that the precursor for de novo synthesis of inositol 1,3,4,5,6-pentakisphosphate was inositol 1,3,4,6-tetrakisphosphate. Bombesin stimulated the net breakdown of inositol 1,3,4,5,6-pentakisphosphate and increased the level of inositol 3,4,5,6-tetrakisphosphate; the relative specific radioactivities of these two compounds were similar under all conditions. These data led to the novel proposal that inositol 3,4,5,6-tetrakisphosphate is the product of inositol 1,3,4,5,6-pentakisphosphate breakdown. This reaction was apparently stimulated by a regulated change in the enzyme(s) which interconvert inositol 1,3,4,5,6-pentakisphosphate and inositol 3,4,5,6-tetrakisphosphate.</description><subject>Animals</subject><subject>bombesin</subject><subject>Bombesin - pharmacology</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Inositol - metabolism</subject><subject>Inositol 1,4,5-Trisphosphate - metabolism</subject><subject>inositol 3,4,5,6-tetrakisphosphate</subject><subject>Inositol Phosphates - metabolism</subject><subject>Kinetics</subject><subject>myo-inositol 1,3,4,5,6-pentakisphosphate</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Rats</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkd1qHCEYhqW0pNu0lxDwoJQWdlI_HR09LCFpC4EcJIWeic44uzYzOlWXsFeZW8psdhtII4jg9_4oD0InQE6BgPh6TQiFSlEuP4P6wiRvaEVfoQUQySrG4fdrtHiSvEXvcv5D5lUrOEJHlHFZc7FA91fJr3zIOPZ43MbKh5h9iQMuriRz6_O0jvM2xWXsAzarGHwuVS5-3AzzbYeTKXgyoU3OlDga3LphyKf4-qDwMWC7xTaO1uU54f8eWLJlveRLUU0ulGeN2M6Zt128C7jE565_nhevfI_e9GbI7sPhPEa_Ls5vzn5Ul1fff559u6xaRgWtoDUCQDLekK411hjV1co4qogUDUBN24bXzJGOWAW94KxnzCnDrZVM2bpmx-jTPndK8e_G5aJHn3dfN8HFTdbApZSUqFnI98I2xZyT6_WU_GjSVgPRO5D6EaTeUdKg9CNITWffyaFgY0fXPbkO5Ob5x_187VfrO5-ctj62azdqKvguCABEwx4AXsypQg</recordid><startdate>19900705</startdate><enddate>19900705</enddate><creator>F S Menniti</creator><creator>K G Oliver</creator><creator>K Nogimori</creator><creator>J F Obie</creator><creator>S B Shears</creator><creator>J W Putney, Jr</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope></search><sort><creationdate>19900705</creationdate><title>Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate</title><author>F S Menniti ; K G Oliver ; K Nogimori ; J F Obie ; S B Shears ; J W Putney, Jr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3262-1ca61183570dcabaa9d49ae2908671142c7543e0d0b91f653f33e9a5bb839b443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>bombesin</topic><topic>Bombesin - pharmacology</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Inositol - metabolism</topic><topic>Inositol 1,4,5-Trisphosphate - metabolism</topic><topic>inositol 3,4,5,6-tetrakisphosphate</topic><topic>Inositol Phosphates - metabolism</topic><topic>Kinetics</topic><topic>myo-inositol 1,3,4,5,6-pentakisphosphate</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Rats</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>F S Menniti</creatorcontrib><creatorcontrib>K G Oliver</creatorcontrib><creatorcontrib>K Nogimori</creatorcontrib><creatorcontrib>J F Obie</creatorcontrib><creatorcontrib>S B Shears</creatorcontrib><creatorcontrib>J W Putney, Jr</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>F S Menniti</au><au>K G Oliver</au><au>K Nogimori</au><au>J F Obie</au><au>S B Shears</au><au>J W Putney, Jr</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1990-07-05</date><risdate>1990</risdate><volume>265</volume><issue>19</issue><spage>11167</spage><epage>11176</epage><pages>11167-11176</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>In the rat pancreatoma cell line, AR4-2J, three inositol tetrakisphosphate isomers were identified, (1,3,4,6), (1,3,4,5), (3,4,5,6), which were increased during activation of phospholipase C by bombesin. Two other isomers were identified, (1,4,5,6) and a fifth isomer which was either (1,2,3,4) or (1,2,3,6), which have not previously been detected in any cell type. To study the metabolic interrelationships between these compounds and inositol 1,3,4,5,6-pentakisphosphate in the intact cell, their turnover was assessed under different protocols of [3H]myo-inositol labeling; the inositol phosphates were labeled to near steady state or under conditions where either rapidly or slowly turning over inositol polyphosphates were preferentially labeled. The relative specific radioactivities of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, inositol 1,3,4-trisphosphate, and inositol 1,3,4,6-tetrakisphosphate were very similar in bombesin-stimulated cells, consistent with the pathway for the conversion of inositol 1,4,5-trisphosphate to the other three inositol polyphosphates. Compared with these inositol phosphates, the turnover of inositol 1,3,4,5,6-pentakisphosphate was slow. An accumulation of radioactivity into inositol 1,3,4,5,6-pentakisphosphate was observed only under labeling conditions where its relative specific radioactivity was substantially below that of inositol 1,3,4,6-tetrakisphosphate. This indicated that the precursor for de novo synthesis of inositol 1,3,4,5,6-pentakisphosphate was inositol 1,3,4,6-tetrakisphosphate. Bombesin stimulated the net breakdown of inositol 1,3,4,5,6-pentakisphosphate and increased the level of inositol 3,4,5,6-tetrakisphosphate; the relative specific radioactivities of these two compounds were similar under all conditions. These data led to the novel proposal that inositol 3,4,5,6-tetrakisphosphate is the product of inositol 1,3,4,5,6-pentakisphosphate breakdown. This reaction was apparently stimulated by a regulated change in the enzyme(s) which interconvert inositol 1,3,4,5,6-pentakisphosphate and inositol 3,4,5,6-tetrakisphosphate.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>2358456</pmid><doi>10.1016/S0021-9258(19)38572-2</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
bombesin
Bombesin - pharmacology
Chromatography, High Pressure Liquid
Inositol - metabolism
Inositol 1,4,5-Trisphosphate - metabolism
inositol 3,4,5,6-tetrakisphosphate
Inositol Phosphates - metabolism
Kinetics
myo-inositol 1,3,4,5,6-pentakisphosphate
Pancreatic Neoplasms - metabolism
Rats
Tumor Cells, Cultured
title Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate
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