Thromboxane A2 receptor-mediated tonic contraction is attributed to an activation of phosphatidylcholine-specific phospholipase C in rabbit aortic smooth muscles.
Thromboxane A2 (TXA2) analogue STA2 produced a tonic contraction in rabbit aortic smooth muscles. In the present study, we examined phosphatidylcholine (PC) hydrolysis as a signaling pathway for the tonic contraction in rabbit aortic smooth muscles. In the primary cultured cells labeled with [3H]choline, STA2 caused an accumulation of [3H]phosphorylcholine, a metabolite of PC by PC-specific PLC, in a concentration-dependent manner. The accumulation of [3H]phosphorylcholine was inhibited by SQ29548, a TXA2 receptor antagonist. In the muscle strips, STA2-induced tonic contraction was potently inhibited by D609, an inhibitor of PC-specific phospholipase C in a concentration-dependent manner with the IC50 of about 10 microM. Norepinephrine-induced tonic contraction was also inhibited by D609 with a weaker potency. These results strongly suggest that stimulation of TXA2 receptor results in the activation of PC-specific phospholipase C to yield diacylglycerol that contributes to the tonic contraction.
Nakahata
N
N
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Sendai, Japan.
Takano
H
H
Ohizumi
Y
Y
D000818:Animals; D001011:Aorta; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D009636:Norbornanes; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D009636:Norbornanes; D010713:Phosphatidylcholines; D017482:Receptors, Thromboxane; D013859:Thiocarbamates; D013871:Thiones; D010767:Phosphorylcholine; D015240:Phorbol 12,13-Dibutyrate; D013928:Thromboxane A2; C046498:tricyclodecane-9-yl-xanthogenate; C076068:ONO 11006; C045749:SQ 29548; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D009638:Norepinephrine