guanosine-diphosphate and lysophosphatidylinositol

1. A pharmacological characterization was made of the effects of lysophosphatidyl-inositol (lysoPI) and -ethanolamine (lysoPE) on the Ca(2+)-sensitivity of contraction in alpha-toxin permeabilized rat mesenteric arteries. The effect of GTP gamma S (G-protein activator), diacylglycerols (DAGs, dioctanoyl glycerol (diC8) and 1-stearoyl-2-arachidonoyl-sn-glycerol) and phorbol myristate acetate (PMA, protein kinase C (PKC) activator) on Ca(2+)-sensitivity was also assessed. 2. LysoPI increased the Ca(2+)-sensitivity, demonstrated by both an increase in tension induced by 1 microM [Ca2+]free and an increase in the Ca(2+)-sensitivity of Ca2+ concentration-tension curves. LysoPE did not enhance force or Ca(2+)-sensitivity. 3. GTP gamma S enhanced force at constant Ca2+, increased the Ca(2+)-sensitivity, and increased force under Ca(2+)-free conditions. PMA also increased force at constant Ca2+ and increased Ca(2+)-sensitivity, but caused no force development under Ca(2+)-free conditions. 4. DAGs, both diC8 and the more physiological relevant DAG, 1-stearoyl-2-arachidonoyl-sn-glycerol, enhanced force at constant Ca2+ and increased the Ca(2+)-sensitivity. DiC8, in contrast to 1-stearoyl-2-arachidonoyl-sn-glycerol, caused force development under Ca(2+)-free conditions and substantially enhanced force at maximal Ca(2+)-induced contraction. GDP-beta-S abolished the increased Ca(2+)-sensitization induced by noradrenaline, but not that by DAGs. 5. The PKC inhibitor calphostin C completely abolished Ca(2+)-sensitization induced by all of the Ca(2+)-sensitizing agents. 6. These results show that lysoPI can increase the Ca(2+)-sensitivity of smooth muscle contraction, and the Ca(2+)-sensitization induced by DAGs was not completely G-protein mediated, because it was not inhibited by GDP-beta-S. A central role for PKC in regulation of Ca(2+)-sensitization in rat mesenteric small arteries was indicated by the abolishment of Ca(2+)-sensitization by calphostin C.

Topics: Animals; Calcium; Diglycerides; GTP-Binding Proteins; Guanosine Diphosphate; Guanosine Triphosphate; Lysophospholipids; Mesenteric Arteries; Muscle Contraction; Muscle, Smooth, Vascular; Naphthalenes; Norepinephrine; Permeability; Protein Kinase C; Rats; Sensitivity and Specificity; Tetradecanoylphorbol Acetate; Thionucleotides; Type C Phospholipases