Stimulation of phospholipase C-mediated hydrolysis of phosphoinositides by adenosine 5'-triphosphate via P2-purinoceptors in cultured rat aortic vascular smooth muscle cells.
Incubation of [3H] inositol-labeled cultured rat aortic vascular smooth muscle cells with angiotensin II caused the dose- and time-dependent formation of inositol mono-, bis- and trisphosphates. Under these conditions, adenosine triphosphate (ATP) stimulated the formation of these inositol phosphates. The maximal reaction velocities obtained by ATP and angiotensin II were roughly the same. The doses of ATP giving half maximal and maximal reaction velocities were about 100 microM and 1 mM, respectively. This action of ATP was mimicked by other nucleotides such as adenosine diphosphate (ADP) and guanosine triphosphate (GTP), but these nucleotides were far less effective than ATP. Adenosine monophosphate (AMP), adenosine, guanosine diphosphate (GDP), guanosine monophosphate (GMP), deoxythymidine trisphosphate (dTTP), and cytosine triphosphate (CTP) were almost ineffective. The formation of inositol phosphates induced by ATP was inhibited partially by pretreatment of the cells with pertussis toxin. This toxin ADP-ribosylated a protein with a molecular mass of about 40,000. These results indicate that ATP induced the phospholipase C-mediated hydrolysis of phosphoinositides probably via P2-purinoceptors in rat aortic vascular smooth muscle cells, and suggest that a pertussis toxin-sensitive GTP-binding protein is involved at least partially in the coupling of this receptor to the phospholipase C in this cell type.
Tsuda
T
T
Department of Internal Medicine (1st Division), Kobe University School of Medicine, Japan.
Kawahara
Y
Y
Fukumoto
Y
Y
Takai
Y
Y
Fukuzaki
H
H
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins