Involvement of K(+) channels in the relaxant effects of YC-1 in vascular smooth muscle.
This study addresses the question whether K(+) channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1 ). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 microM) more potently than those induced by K(+)(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 microM), and iberiotoxin (0.1 microM), but not glibenclamide (10 microM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 microM) induced a hyperpolarisation which was antagonised by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ; 50 microM). In rat aorta, YC-1 (30 microM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 microM), but inhibited by ODQ (50 microM) or charybdotoxin (0.2 microM). In smooth muscle cells from rat aorta, YC-1 (10 microM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K(+) channels.
Seitz
S
S
Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Str. 67, D-55101, Mainz, Germany.
Wegener
J W
JW
Rupp
J
J
Watanabe
M
M
Jost
A
A
Gerhard
R
R
Shainberg
A
A
Ochi
R
R
Nawrath
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D007191:Indazoles; D015221:Potassium Channels; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D010656:Phenylephrine; D011188:Potassium