2 DIFFERENT TYPES OF CHANNELS ARE TARGETS FOR POTASSIUM CHANNEL OPENERS IN XENOPUS OOCYTES

被引:22
作者
HONORE, E
LAZDUNSKI, M
机构
[1] Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, 660 route des Lucioles, Sophia Antipolis
关键词
FOLLICULAR XENOPUS OOCYTE; POTASSIUM CHANNEL OPENER; GLIBENCLAMIDE; ATP-SENSITIVE POTASSIUM CHANNEL;
D O I
10.1016/0014-5793(91)80019-Y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
K+ channel openers elicit K+ currents in follicle-enclosed Xenopus oocytes. The most potent activators are the pinacidil derivatives P1075 and P1060. The rank order of potency to activate K+ currents in follicle-enclosed oocytes was: P1075 (K0.5:5-mu-M) > P1060 (K0.5:12-mu-M) > BRL38227 (lemakalim) (K0.5:77-mu-M) > RP61419 (K0.5:100-mu-M) > (-)pinacidil (K0.5:300-mu-M). Minoxidil sulfate, nicorandil, RP49356 and diazoxide were ineffective. Activation by the K+ channel openers could be abolished by the antidiabetic sulfonylurea glibenclamide. It was not affected by the blocker of the Ca2+-activated K+ channels charybdotoxin. The various K+ channel openers failed to activate glibenclamide-sensitive K+ channels in defolliculated oocytes, but BRL derivatives (K0.5 for BRL38226 is 150-mu-M) and RP61419 inhibited a background current. The channel responsible for this background current is K+ permeable but not fully selective for K+. It is resistant to glibenclamide. It is inhibited by Ba2+, 4-aminopyridine, Co2+, Ni2+ and La3+.
引用
收藏
页码:75 / 79
页数:5
相关论文
共 17 条
[1]   ELECTRICAL AND MECHANICAL EFFECTS OF BRL34915 IN GUINEA-PIG ISOLATED TRACHEALIS [J].
ALLEN, SL ;
BOYLE, JP ;
CORTIJO, J ;
FOSTER, RW ;
MORGAN, GP ;
SMALL, RC .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 89 (02) :395-405
[2]   ENHANCEMENT OF POTASSIUM-SENSITIVE CURRENT IN HEART-CELLS BY PINACIDIL - EVIDENCE FOR MODULATION OF THE ATP-SENSITIVE POTASSIUM CHANNEL [J].
ARENA, JP ;
KASS, RS .
CIRCULATION RESEARCH, 1989, 65 (02) :436-445
[3]  
BERNARDI H, 1989, ARZNEIMITTEL-FORSCH, V39-1, P159
[5]  
Cook NS, 1989, POTASSIUM CHANNELS S, P181
[6]   POTASSIUM SELECTIVE ION CHANNELS IN INSULIN-SECRETING CELLS - PHYSIOLOGY, PHARMACOLOGY AND THEIR ROLE IN STIMULUS-SECRETION COUPLING [J].
DUNNE, MJ ;
PETERSEN, OH .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1071 (01) :67-82
[7]   STRUCTURE-ACTIVITY-RELATIONSHIPS OF K+ CHANNEL OPENERS [J].
EDWARDS, G ;
WESTON, AH .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1990, 11 (10) :417-422
[8]  
FOSSET M, 1988, J BIOL CHEM, V263, P7933
[9]   CROMAKALIM, NICORANDIL AND PINACIDIL - NOVEL DRUGS WHICH OPEN POTASSIUM CHANNELS IN SMOOTH-MUSCLE [J].
HAMILTON, TC ;
WESTON, AH .
GENERAL PHARMACOLOGY, 1989, 20 (01) :1-9
[10]  
HONORE E, 1991, IN PRESS P NATL ACAD