Inhibition by docosahexaenoic acid of receptor-mediated Ca(2+) influx in rat vascular smooth muscle cells stimulated with 5-hydroxytryptamine.
The effect of docosahexaenoic acid treatment on intracellular Ca(2+) dynamics in rat vascular smooth muscle cells stimulated with 5-hydroxytryptamine (5-HT) has been investigated in order to elucidate one of the mechanisms for its beneficial effect on cardiovascular disorders. The treatment of cells with 30 microM docosahexaenoic acid for 2 days inhibited an increase in intracellular Ca(2+) concentration induced by 5-HT (10 microM) and a depolarizing concentration of KCl (80 mM). Docosahexaenoic acid treatment significantly inhibited divalent cation influx stimulated by 5-HT and KCl, as measured by Mn(2+) quenching method, whereas had no effect on 5-HT-induced Ca(2+) release from the internal stores. Docosahexaenoic acid treatment also significantly inhibited 5-HT receptor-mediated Ca(2+) influx through Ni(2+)-insensitive channels that were distinct from store-operated channels. These results suggest that the specific inhibition of intracellular Ca(2+) dynamics in vascular smooth muscle cells may contribute to the beneficial properties of docosahexaenoic acid on cardiovascular disorders.
Hirafuji
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. hirafuji@hoku-iryo-u.ac.jp
Ebihara
T
T
Kawahara
F
F
Hamaue
N
N
Endo
T
T
Minami
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008345:Manganese / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D015220:Calcium Channels; D011985:Receptors, Serotonin; D004281:Docosahexaenoic Acids; D012701:Serotonin; D008345:Manganese; D011189:Potassium Chloride; D009532:Nickel; D002118:Calcium