title: Change of Ca2+ requirement for myosin phosphorylation by prostaglandin F2 alpha.
abstract: The mechanism of contraction of vascular smooth muscle by prostaglandin F2 alpha (PGF2 alpha) was examined by simultaneous measurement of the intracellular Ca2+ concentration [( Ca2+]i), force, and myosin light-chain (MLC) phosphorylation in ferret aorta. In the presence of 2.5 mM extracellular Ca2+, PGF2 alpha (10(-5)M) produced a tonic contraction with a transient spike in [Ca2+]i, followed by a relatively small sustained increase in [Ca2+]i (from a basal level of 2.32 +/- 0.07 x 10(-7) to 2.72 +/- 0.05 x 10(-7) M). In Ca(2+)-free bathing media, PGF2 alpha also produced a tonic contraction with a small spike in [Ca2+]i, indicating a release of Ca2+ from intracellular store sites, followed by no significant increase in [Ca2+]i. Ca(2+)-force curves were constructed by plotting the calibrated steady-state aequorin light signal against the resulting steady-state force. The curve was significantly shifted to the left by PGF2 alpha. PGF2 alpha also shifted the Ca(2+)-phosphorylation curve to the left. These results suggest that PGF2 alpha causes contraction by both elevating [Ca2+]i and decreasing the Ca2+ requirement for MLC phosphorylation. The data are consistent with a mechanism where there is either an increase in activity of MLC kinase or a decrease in phosphatase activity. Additionally, there was a smaller, but statistically significant, effect to increase force at any one phosphorylation level, pointing to the possibility of regulation of contractile force separate from MLC phosphorylation.
authors.affiliation: Cardiovascular Division, Charles A. Dana Research Institute, Boston, Massachusetts.
authors.forename: E
authors.initials: E
authors.lastname: Suematsu
authors.forename: M
authors.initials: M
authors.lastname: Resnick
authors.forename: K G
authors.initials: KG
authors.lastname: Morgan
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D015237:Dinoprost / Q000378:metabolism*; D005289:Ferrets; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009218:Myosins / Q000378:metabolism*; D009994:Osmolar Concentration; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D012044:Regression Analysis
chemical_list: D015237:Dinoprost; D009218:Myosins; D011188:Potassium; D002118:Calcium