Myosin phosphorylation-independent contraction induced by phorbol ester in vascular smooth muscle.
In isolated rat aorta, carotid artery, tail artery, rabbit aorta and mesenteric artery, but not in ear artery, 1 microM 12-deoxyphorbol 13-isobutyrate (DPB) induced a sustained contraction. However, DPB increased cytosolic Ca++ concentration ([Ca++]i) only in rat aorta and carotid artery. Similar results were obtained with phorbol 12,13-dibutyrate, although the inactive phorbol ester, 4-alpha-phorbol 12,13-dibutyrate, was ineffective. In rat aorta, DPB-induced contraction was followed by an increase in 20 kDa myosin light chain (MLC) phosphorylation. Both contraction and MLC phosphorylation stimulated by DPB were greater than those due to high K+ for a given increase in [Ca++]i. A Ca++ channel blocker, verapamil, decreased the DPB-induced increments in [Ca++]i and MLC phosphorylation to their respective resting levels, although contraction was inhibited only slightly. In the absence of external Ca++ (with 0.5 mM ethyleneglycol bis(beta-aminoethyl-ether)tetraacetic acid), DPB induced sustained contraction without increasing [Ca++]i or MLC phosphorylation. This contraction was followed by an increase in stiffness and force recovery after a shortening step. These results suggest that the contraction induced by DPB in rat aorta is due to increase in [Ca++]i followed by MLC phosphorylation and Ca++ sensitization of MLC phosphorylation. In the presence of verapamil or in the absence of external Ca++, DPB may increase cross-bridge cycling by activating an unknown mechanism that is not dependent on an increase in MLC phosphorylation.
Sato
K
K
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Hori
M
M
Ozaki
H
H
Takano-Ohmuro
H
H
Tsuchiya
T
T
Sugi
H
H
Karaki
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009218:Myosins / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D010703:Phorbol Esters; D014700:Verapamil; D009218:Myosins; D002118:Calcium