Linked Life Data

7511340

Source:http://linkedlifedata.com/resource/pubmed/id/7511340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 1
pubmed:dateCreated
1994-4-28
pubmed:abstractText
Genistein, a tyrosine kinase inhibitor, inhibited cholecystokinin (CCK)-induced maximal amylase release from rat pancreatic acini by 18, 31, and 46% at concentrations of 100, 300, and 750 microM, respectively, after 30 min preincubation. Genistein similarly decreased amylase release stimulated by bombesin but not that stimulated by secretin or vasoactive intestinal peptide. The steps of stimulus-secretion coupling affected by genistein were further evaluated. We found genistein dose dependently suppressed CCK-as well as NaF-induced polyphosphoinositide hydrolysis with a 50% inhibitory concentration of 380 and 400 microM, respectively, but only slightly suppressed the increase of intracellular Ca2+ concentration in response to either low or high concentrations of CCK. Genistein at 300 microM also decreased incorporation of [3H]inositol into phosphatidylinositol 4,5-bisphosphate. Most strikingly, 300 microM genistein inhibited Ca(2+)-stimulated amylase release by 85% in streptolysin O-permeabilized acini and thapsigargin-stimulated amylase release by 69% in intact acini. Daidzein, the inactive analogue of genistein, had no effect on any of the above parameters. Genistein, up to 750 microM, did not affect amylase release in response to phorbol ester. To relate these inhibitory effects of genistein to its inhibition of tyrosine phosphorylation, Western blotting was performed with an anti-phosphotyrosine monoclonal antibody. Genistein at 100 microM partly and at 300 microM completely inhibited CCK-induced tyrosine phosphorylation. In conclusion, genistein inhibits amylase release at multiple stages of stimulus-secretion coupling. These effects most likely involve both tyrosine kinase-dependent and -independent mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G303-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Multiple inhibitory effects of genistein on stimulus-secretion coupling in rat pancreatic acini.
pubmed:affiliation
Department of Physiology, University of Michigan, Ann Arbor 48109-0622.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't