Role of protein kinase C in endothelin-1-induced contraction of human myometrium.
The role of protein kinase C (PKC) in the contraction of human myometrium induced by endothelin-1 was investigated. The PKC inhibitor, calphostin C, reduced the sustained phase of endothelin-1-induced contraction. The expression and subcellular distribution of PKC isoforms were determined in unstimulated myometrium by Western blotting using isoform-specific antisera. At least five PKC isoforms (PKCalpha, PKCbeta1, PKCbeta2, PKCzeta, and trace amounts of PKCepsilon) were detected. Quantitative immunoblotting revealed that all these isoforms were diversely distributed between the cytosolic and particulate fractions. After stimulation with phorbol 12,13-dibutyrate (PDB) and endothelin-1, differential redistribution occurred, suggesting a selective role of these isoforms in the physiological function of the myometrium. Biochemical assay confirmed that PDB as well as endothelin-1 evoked a decrease in cytosolic PKC activity. Taken together, these results suggest that PKC may play a role in endothelin-1-induced contraction of human uterine smooth muscle.
Institut National de la Santé et de la Recherche Médicale, Unité 361, Université René-Descartes, Paris, France. u361@cochin.inserm.fr
M
M
Breuiller-Fouché
C
C
Tertrin-Clary
V
V
Héluy
T
T
Fournier
F
F
Ferré
D000328:Adult; D003600:Cytosol / Q000201:enzymology; D019332:Endothelin-1 / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008875:Middle Aged; D009215:Myometrium / Q000201:enzymology* / Q000648:ultrastructure; D009281:Naphthalenes / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D014590:Uterine Contraction / Q000502:physiology*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009281:Naphthalenes; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C058819:calphostin C