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

The pharmacological and molecular properties of ATP-sensitive K+ channels p resent in pig detrusor smooth muscle were investigated. In isolated pig det rusor strips, ATP-sensitive K+ channel openers inhibited contractions elici ted by low frequency field-stimulation in a concentration-dependent manner. The inhibitory effects of P1075 [N-cyano-N'-(1,1-dimethylpropyl)-N "-3-pyr idylguanidine] were attenuated by glyburide with a pA(2) value of 7.38 (slo pe = 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 r elaxation of the pre-contracted (25 mM potassium chloride, KCl) human detru sor (r = 0.95). Reverse transcriptase polymerase chain reaction (RT-PCR) an alysis showed the presence of mRNA for sulfonylurea receptors SUR1 and SUR2 B in both pig and human detrusor. Considering the similarities in the molec ular and pharmacological profile of ATP-sensitive K+ channels between the p ig 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 Sc ience B.V. All rights reserved.