Pharmacological and molecular analysis of ATP-sensitive K+ channels in the pig and human detrusor

被引:60
作者
Buckner, SA [1 ]
Milicic, I [1 ]
Daza, A [1 ]
Davis-Taber, R [1 ]
Scott, VES [1 ]
Sullivan, JP [1 ]
Brioni, JD [1 ]
机构
[1] Abbott Labs, Div Pharmaceut Prod, Abbott Pk, IL 60064 USA
关键词
K+ channel opener; detrusor smooth muscle; smooth muscle relaxation; K plus channels; ATP-sensitive; sulfonylurea receptor;
D O I
10.1016/S0014-2999(00)00388-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The pharmacological and molecular properties of ATP-sensitive K+ channels present in pig detrusor smooth muscle were investigated. In isolated pig detrusor strips, ATP-sensitive K+ channel openers inhibited contractions elicited by low frequency field-stimulation in a concentration-dependent manner. The inhibitory effects of P1075 [N-cyano-N'-(1,1-dimethylpropyl)-N "-3-pyridylguanidine] were attenuated by glyburide with a pA(2) value of 7.38 (slope = 1.08). The potency of the inhibitory effects of the K+ channel openers on the field-stimulated contractions correlated well with those evoked by the muscarinic receptor agonist, carbachol (r = 0.93) and furthermore, to relaxation of the pre-contracted (25 mM potassium chloride, KCl) human detrusor (r = 0.95). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed the presence of mRNA for sulfonylurea receptors SUR1 and SUR2B in both pig and human detrusor. Considering the similarities in the molecular and pharmacological profile of ATP-sensitive K+ channels between the pig and the human detrusor, it is concluded that the pig detrusor may serve as a suitable in vitro model for the evaluation of novel K+ channel openers with potential use in urological disorders in humans. (C) 2000 Elsevier Science B.V. All rights reserved.
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页码:287 / 295
页数:9
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