RT Journal Article
SR Electronic
T1 Ca++ utilization in the constriction of rat aorta to stimulation of protein kinase C by phorbol dibutyrate.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 934
OP 939
VO 242
IS 3
A1 A T Chiu
A1 J M Bozarth
A1 M S Forsythe
A1 P B Timmermans
YR 1987
UL http://jpet.aspetjournals.org/content/242/3/934.abstract
AB To determine the role of activated protein kinase C in vascular smooth muscle contraction, phorbol dibutyrate was used to stimulate this enzyme in order to evaluate the source(s) of Ca++ (10(-8) to 3 X 10(-6) M) elicited a concentration-dependent sustained contraction which was slow in onset but progressive in developed tension. The maximal contractile response induced by phorbol dibutyrate was only partly dependent on influx of extracellular Ca++ as shown by similar reductions (40%) produced by Ca++-free buffer, LaCl3 (1 mM) or nifedipine (10(-6) M). These data suggest that phorbol dibutyrate is able to open Ca++ channels which are sensitive to nifedipine blockade. However, unlike norepinephrine or K+-depolarization, phorbol dibutyrate evoked a slow 45Ca++ influx which occurred only after extended contact time. Pretreatment with nifedipine again abolished this response. In contrast to norepinephrine, phorbol dibutyrate did not cause 45Ca++ efflux indicating that intracellular Ca++ was not mobilized. It is concluded that the residual 60% contraction to phorbol dibutyrate most likely occurs via a mechanism independent of the Ca-calmodulin pathway.