Effects of prostaglandin E1 on vascular ATP-sensitive potassium channels.
BACKGROUND
Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive potassium (KATP) channels, which induces vasorelaxation. However, direct evidence of PGE1 interactions with vascular KATP channels is limited.


METHODS
The present study investigated the effects and mechanisms of PGE1 on vascular KATP channels in both isometric tension and patch clamp experiments. Isometric tension experiments were performed in rat thoracic aortic rings without an endothelium. Electrophysiologic experiments were performed using patch-clamp techniques to monitor KATP channels in rat vascular smooth muscle cells.


RESULTS
PGE1 significantly decreased the isometric tension in a concentration-dependent manner, which was partially inhibited by pretreating with a KATP channel inhibitor, glibenclamide (1 microM), or an inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). Application of PGE1 to the bath solution during cell-attached recordings induced a significant increase in KATP channel activity, whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1-induced KATP channel currents in cell-attached patches were abolished by pretreating with Rp-cAMPS (100 microM).


CONCLUSIONS
The results indicate that the activation of vascular KATP channels played an important role in the PKA-dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological experiment demonstrated that PGE1 activated vascular KATP channels via PKA activation.
Eguchi
Satoru
S
Department of Dental Anesthesiology, Tokushima University School of Dentistry, Tokushima, Japan.
Kawano
Takashi
T
Yinhua
Tanaka
Katsuya
K
Yasui
Sonoko
S
Mawatari
Kazuaki
K
Takahashi
Akira
A
Nakaya
Yutaka
Y
Oshita
Shuzo
S
Nakajo
Nobuyoshi
N
D000465:Algorithms; D000527:Alprostadil / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D054086:KATP Channels; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; D014665:Vasodilator Agents; D005576:Colforsin; D010656:Phenylephrine; C016957:adenosine-3',5'-cyclic phosphorothioate; D020110:Pinacidil; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000527:Alprostadil; D005905:Glyburide