Phasic and tonic components in 5-HT2 receptor-mediated rat aorta contraction: participation of Ca++ channels and phospholipase C.
The mechanisms of 5-hydroxytryptamine (5-HT)-induced contraction of rat aorta were investigated in vitro. The 5-HT-induced contraction could be analyzed into two distinct components (phasic and tonic) by the use of appropriate inhibitors; nifedipine, an inhibitor of voltage-dependent Ca++ channels, inhibited only the phasic component of 5-HT-induced contraction while totally blocking the KCl-induced contraction. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate, an inhibitor of phospholipase C, inhibited the tonic components of 5-HT-induced contraction as well as the 5-HT-induced stimulation of phosphoinositide hydrolysis in rat aorta. This component of contraction was mimicked by a protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate. These results suggest that 5-HT2 receptors differentially regulate a voltage-dependent Ca++ channel and phospholipase C activity; the voltage-dependent Ca++ channel is involved in the phasic component of contraction whereas the phosphoinositide hydrolysis that results in the activation of protein kinase C and calcium mobilization by inositol triphosphate plays a physiologically important role in the tonic component of the aortic contraction.
Nakaki
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T
Roth
B L
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Chuang
D M
DM
Costa
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E
D000818:Animals; D001011:Aorta / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology; D006868:Hydrolysis; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D048448:Phenylcarbamates; D010716:Phosphatidylinositols / Q000378:metabolism; D010740:Phospholipases / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D002219:Carbamates; D007473:Ion Channels; D048448:Phenylcarbamates; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D010740:Phospholipases; D010738:Type C Phospholipases; D009543:Nifedipine; D002118:Calcium