Protein kinase C potentiates stretch-induced cerebral artery tone by increasing intracellular sensitivity to Ca2+.
The effects of PMA, an activator of protein kinase C, was studied on Ca2+-induced tone in the rabbit basilar artery. Contractile responses to Ca2+ occurred only in arteries pretreated with PMA; the extent of Ca2+-induced contractions were related to the level of stretch applied to the vessels. Bay K 8644, a Ca2+-channel agonist, at a concentration that was subthreshold for contraction, augmented the extent of Ca2+-induced tone occurring in PMA-treated arteries. Nifedipine, a Ca2+-entry inhibitor, and staurosporine, an inhibitor of protein kinase C attenuated the response to Ca2+ occurring either in the absence or presence of Bay K 8644. Our results suggest that PMA increases myofilament sensitivity to Ca2+, such that levels of Ca2+ previously ineffective for contraction Ca2+-influx, e.g. due to Bay K 8644, is manifest as contraction. Our results also confirm the role of extracellular Ca2+ entry via plasma membrane stretch-dependent Ca2+-channels in the maintenance of vascular tone in the basilar artery.
Laher
I
I
Department of Pharmacology, University of Vermont, Burlington 05405.
Vorkapic
P
P
Dowd
A L
AL
Bevan
J A
JA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D019311:Staurosporine; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium