Effects of PKC downregulation on norepinephrine- and prostaglandin F2 alpha-induced contraction in rat aorta.
The purpose of this study was to investigate, through phorbol ester-induced protein kinase C (PKC) downregulation, the role of PKC in the regulation of alpha-adrenergic agonist- and prostaglandin (PG) F2 alpha-induced contraction in vascular smooth muscle. In rat aorta, long-term phorbol ester exposure (10 microM phorbol dibutyrate for 17 h), a procedure that decreased PKC activity by > 95%, and maximal phorbol myristate acetate (PMA)-induced contraction by approximately 75%, decreased tissue sensitivity to norepinephrine (NE) and PGF2 alpha 2.8- and 4.6-fold, respectively, while maximal contraction was not significantly decreased. In contrast, long-term phorbol ester exposure did not alter tissue sensitivity to KCl, while maximal KCl contraction was decreased by 40%. Long-term phorbol ester exposure, as well as short-term phorbol ester exposure (1 microM PMA for 1 h), abolished the initial transient NE contraction elicited in Ca(2+)-free solution. In contrast, long-term phorbol ester exposure did not alter the plateau NE or PGF 2 alpha contraction elicited in Ca(2+)-free solution. Short-term phorbol ester exposure of PKC-downregulated tissues potentiated the plateau PGF2 alpha contraction elicited in Ca(2+)-free solution, although the magnitude of potentiation was less than that observed in non-PKC downregulated tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Rapoport
R M
RM
Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Ohio, USA.
Campbell
A K
AK
Bazan
E
E
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction
D011460:Prostaglandins F; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002118:Calcium; C100006:prostaglandin F1; D009638:Norepinephrine