Sustained contraction of vascular smooth muscle: calcium influx or C-kinase activation?
We have investigated the relative contributions of Ca++ influx and C-kinase activation to the sustained contraction of smooth muscle of rabbit aorta. In physiological salt solution (PSS), the alpha adrenergic agonist, phenylephrine (PhE), induced a rapid initial contraction followed by a maintained tonic contraction whereas the C-kinase activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), caused only a slow tonic contractile response. Both PhE- and TPA-induced contractions were accompanied by a significant increase in the unidirectional 45Ca influx. The tonic phase of PhE contraction and the slow contractile response of TPA also were reduced, but not abolished completely in Ca++-free solution containing 2 mM ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid. In addition, the relatively specific C-kinase inhibitor, H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], reversibly inhibited the TPA-induced contraction in PSS and almost abolished the TPA response in Ca++-free solution. On the other hand, H-7 caused only partial inhibition (30.2% +/- 4.09, n = 5) of the PhE sustained contraction in PSS and abolished completely the residual PhE maintained response in Ca++-free solution. The H-7 inhibition of the PhE sustained contraction was reversible in both PSS and Ca++-free solution. Furthermore, TPA alone could not maintain the contractile response initiated by a high K+ depolarizing solution upon replacement of the high K+ solution by normal PSS. These findings emphasize the importance of Ca++ influx and suggest only a minor role of C-kinase in maintaining the tonic contraction of vascular smooth muscle.
Khalil
R A
RA
Department of Pharmacology, University of Miami School of Medicine, Florida.
van Breemen
C
C
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction
D007546:Isoquinolines; D010879:Piperazines; D010656:Phenylephrine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium