Linked Life Data

7625829

Source:http://linkedlifedata.com/resource/pubmed/id/7625829

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-8-28
pubmed:abstractText
Genistein, a potent tyrosine kinase inhibitor, inhibits contraction of several types of smooth muscle, suggesting that protein tyrosine phosphorylation may be an important regulatory mechanism for smooth muscle contraction. We suspected that one site between activation of smooth muscle and contraction which might be modulated by protein tyrosine phosphorylation involved mechanisms for control of Ca2+ sensitivity. Since smooth muscle permeabilized with staphylococcal alpha-toxin permits direct assessment of agonist-induced Ca2+ sensitivity, we studied the effects of genistein on potential coupling between tyrosine phosphorylation and Ca2+ sensitivity in permeabilized ileal smooth muscle. Results show that contraction of intact preparations with carbachol is markedly and reversibly inhibited by 40% at 4 micrograms genistein/ml and by 60% at 20 micrograms genistein/ml. Permeabilized preparations that are contracted with a submaximal [Ca2+] in the presence of GTP relax when genistein is added to the medium. Genistein also reversibly inhibits contractions induced in permeabilized muscle with either a submaximal or maximal [Ca2+] in the presence of GTP, as well as receptor-coupled activation of Ca2+ sensitization with 10 microM carbachol/10 microM GTP. Activation of permeabilized preparations at pCa 4.6 in the presence of 100 microM GTP promotes time-dependent tyrosine phosphorylation of several substrates. Both phosphorylation and force are inhibited by genistein. However, relatively high levels of myosin light chain phosphorylation persist during genistein-induced inhibition of Ca2+ sensitivity. In contrast, genistein has no effect on Ca(2+)-activated contraction in Triton-skinned preparations in either the presence or the absence of GTP. This shows that it does not directly inhibit actin-myosin interaction and suggests that its target(s) may be a cytosolic or membrane-bound regulatory protein(s) that is leached from the preparations during Triton-skinning. Taken together, these new data suggest that (a) tyrosine phosphorylation of one or more substrates may be coupled to mechanisms which regulate Ca2+ sensitivity and (b) the inhibitory effects of genistein are probably due to inhibition of agonist-induced Ca2+ sensitivity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
320
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
236-42
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Modulation of Ca2+ sensitivity in smooth muscle by genistein and protein tyrosine phosphorylation.
pubmed:affiliation
II. Physiologisches Institut, Universität Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't