title: Receptor agonists induce myosin phosphorylation-dependent and phosphorylation-independent contractions in vascular smooth muscle.
abstract: In isolated rat aorta, 72.7 mM KCI, 10 microM prostaglandin F2 alpha, 30 nM endothelin-1 and 1 microM norepinephrine increased muscle tension, cytosolic Ca++ concentration ([Ca++]i) and 20 kDa myosin light chain (MLC) phosphorylation. The levels of contractile tension and MLC phosphorylation at a given [Ca++]i were greatest in the presence of endothelin-1 followed by prostaglandin F2 alpha greater than norepinephrine greater than high K+. Verapamil inhibited the high K(+)-induced increments to their respective resting levels. Verapamil also almost completely inhibited the receptor agonist-induced increments in [Ca++]i and MLC phosphorylation, although a part of the contraction was not inhibited. Ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid further decreased [Ca++]i and muscle tension, suggesting that a part of the contraction is regulated by [Ca++]i below a resting level. Receptor agonists induced sustained contraction in the absence of external Ca++ which was not followed by the increase in [Ca++]i or MLC phosphorylation. This contraction was followed by the increments in shortening velocity and stiffness. In the rabbit mesenteric artery permeabilized with Staphylococcus aureus, alpha-toxin, norepinephrine and endothelin-1 shifted the Ca(++)-tension curve to the left in the presence of GTP. From these results, it is suggested that high K(+)-induced sustained contraction of vascular smooth muscle is attributable to an increase in [Ca++]i followed by an increase in MLC phosphorylation. In addition to this fundamental mechanism, receptor agonists increase Ca+ sensitivity of MLC phosphorylation when [Ca++]i is higher than resting level resulting in a greater contraction than that induced by high K+ for a given increase in [Ca++]i.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Sakata
authors.forename: H
authors.initials: H
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Takano-Ohmuro
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Sugi
authors.forename: I
authors.initials: I
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Karaki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009218:Myosins / Q000494:pharmacology*; D009529:Nicardipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
chemical_list: D010703:Phorbol Esters; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D011189:Potassium Chloride; D015237:Dinoprost; D014700:Verapamil; D009529:Nicardipine; D009218:Myosins; D002118:Calcium; D009638:Norepinephrine