Document Detail

Synergistic stimulation of DNA synthesis by bradykinin and vasopressin in Swiss 3T3 cells.
MedLine Citation:
PMID:  8077288     Owner:  NLM     Status:  MEDLINE    
Vasopressin and bradykinin bind to receptors coupled to GTP-binding proteins and rapidly induce polyphosphoinositide breakdown leading to Ca2+ mobilization and activation of protein kinase C. Both peptides are known to induce mitogenesis in the presence of growth factors that act through receptors with intrinsic tyrosine kinase activity. Surprisingly, addition of a combination of vasopressin and bradykinin to Swiss 3T3 cells synergistically stimulates DNA synthesis in the absence of any other growth factors. This effect is induced at nanomolar concentrations of the peptides and could be inhibited by addition of specific receptor antagonists or broad spectrum neuropeptide antagonists. Bradykinin, which stimulates transient activation of protein kinase C, induces DNA synthesis in synergy with substances that cause long-term activation of protein kinase C, like vasopressin or phorbol 12,13-dibutyrate. Down-regulation of protein kinase C inhibited the induction of mitogenesis by the combination of vasopressin and bradykinin, thus demonstrating the importance of long-term activation of this enzyme for DNA synthesis. Analysis of tyrosine phosphorylated proteins of M(r) = 110,000-130,000 and M(r) = 70,000-80,000 revealed a biphasic response after stimulation with bradykinin, whereas the response induced by vasopressin declined after the initial maximum. The combination of bradykinin with vasopressin caused an enhanced and prolonged increase in tyrosine phosphorylation of these proteins as compared with the individual peptides. Inhibition of tyrosine phosphorylation by tyrphostin was paralleled by inhibition of DNA synthesis. Together, these results demonstrate synergistic stimulation of DNA synthesis by bradykinin and vasopressin via prolonged stimulation of multiple signaling pathways and imply that the interactive effects of Ca(2+)-mobilizing peptides on mitogenesis may be more general than previously thought.
K Kiehne; E Rozengurt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  160     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1994-10-05     Completed Date:  1994-10-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  502-10     Citation Subset:  IM    
Imperial Cancer Research Fund, London, United Kingdom.
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MeSH Terms
3T3 Cells
Bradykinin / pharmacology*
DNA / biosynthesis*
Drug Combinations
Drug Synergism
Intracellular Membranes / physiology
Mitogens / pharmacology
Signal Transduction / drug effects
Vasopressins / pharmacology*
Reg. No./Substance:
0/Drug Combinations; 0/Mitogens; 11000-17-2/Vasopressins; 58-82-2/Bradykinin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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