Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-8-21
pubmed:abstractText
The contribution of polyphosphoinositides to muscarinic receptor-stimulated phosphoinositide turnover has been evaluated for intact and digitonin-permeabilized human SK-N-SH neuroblastoma cells. Addition of carbamoylcholine to [3H]inositol-prelabeled intact cells resulted in a rapid (5-10 sec) loss of phosphatidylinositol-4,5-bisphosphate and the concomitant appearance of radiolabeled inositol-1,4,5-trisphosphate, inositol-1,3,4-trisphosphate, and inositol tetrakisphosphate. In the presence of the agonist, production of these inositol polyphosphates remained enhanced for up to 45 min. Inositol mono- and bisphosphates steadily accumulated in response to receptor activation and in the presence of Li+ comprised greater than 95% of agonist-stimulated inositol phosphate formation at incubation times greater than 5 min. The major inositol bisphosphate isomer was the 1,4-species. Of the two inositol monophosphates produced, radioactivity recovered in inositol-4-monophosphate increased continuously, whereas that in the inositol-1-monophosphate/inositol-3-monophosphate fraction was delayed in appearance but thereafter progressively accumulated. Omission of Ca2+ reduced carbamoylcholine-stimulated inositol phosphate release by greater than 50% but did not significantly influence the ratio of inositol monophosphates formed. Upon addition of atropine to agonist-pretreated cells, radioactivity was lost from inositol phosphates in the following order: inositol-1,4,5-trisphosphate greater than inositol-1,3,4-trisphosphate greater than inositol-1,4-bisphosphate = inositol-4-monophosphate greater than inositol-1-monophosphate/inositol-3-monophosphate. Although carbamoylcholine addition to digitonin-permeabilized cells also resulted in a sustained release of inositol monophosphates, relatively more inositol-4-monophosphate was produced in these preparations. Omission of ATP from permeabilized cell incubations inhibited carbamoylcholine-stimulated 'inositol phosphate formation by greater than 70%. Whole homogenates of SK-N-SH cells metabolized added inositol-1,4,5-trisphosphate and inositol-1,4-bisphosphate exclusively to inositol-4-monophosphate, whereas inositol-1,3,4,5-tetrakisphosphate was degraded to inositol-1- or 3-monophosphate. Measurement of inositol trisphosphate 3'-kinase and 5'-phosphatase activities revealed that, following permeabilization, 3'-kinase activity was diminished, whereas that of 5'-phosphatase was enhanced. The results indicate that occupancy of muscarinic cholinergic receptors in SK-N-SH cells elicits a continuous Ca2(+)-dependent breakdown of the polyphosphoinositides rather than of phosphatidylinositol.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Carbachol, http://linkedlifedata.com/resource/pubmed/chemical/Digitonin, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-trisphosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/inositol triphosphate...
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Polyphosphoinositides are the major source of inositol phosphates in carbamoylcholine-stimulated SK-N-SH neuroblastoma cells.
pubmed:affiliation
Neuroscience Laboratory, University of Michigan, Ann Arbor 48104.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.