Force development with inosine triphosphate and uridine triphosphate in chemically skinned vascular smooth muscle.
The contraction of vascular smooth muscle is thought to be regulated by reversible phosphorylation of the 20,000 dalton light chains of myosin, catalyzed by myosin light chain kinase that is dependent on calcium and calmodulin. With phosphorylation, there is a coincident increase in the actin-activated myosin NTPase activity, cross bridge interaction and contractile activity. However, this myosin phosphorylation mechanism may not be the sole factor controlling actin-myosin interaction in vascular smooth muscle. Other mechanisms may function in addition to this myosin-linked regulation. A calcium-insensitive regulation of contraction was observed in helical strips of chemically skinned (Triton X-100) arterial smooth muscle. Millimolar concentrations of inosine triphosphate and uridine triphosphate supported concentration dependent force development in the absence of calcium. Force development was a function of the MgNTP concentration. At high free calcium concentrations, an additional component of force was observed. ITP and UTP, in contrast to ATP, are less effective substrates for the myosin light chain kinase, and their effect on actin-myosin interaction is thus less than that of ATP. They are, however, utilized by the myosin NTPase after treatment by ATP-gamma-S. The efficacy of the substrate for the activated NTPase is greater for UTP than ITP than for ATP.
Geremia
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MM
Department of Physiology, UMDNJ-New Jersey Medical School Newark 07103, USA.
Diecke
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FP
D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D007293:Inosine Triphosphate / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D043583:Nucleoside-Triphosphatase; D010766:Phosphorylation; D051381:Rats; D011921:Rats, Inbred WKY; D014544:Uridine Triphosphate / Q000494:pharmacology*
D007293:Inosine Triphosphate; D000255:Adenosine Triphosphate; D009219:Myosin-Light-Chain Kinase; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D009218:Myosins; D002118:Calcium; D014544:Uridine Triphosphate