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Eur J Pharmacol. 2000 Jul 21;400(2-3):287-95.

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

Author information

1
Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, D47C, Bldg. AP9, First Floor, 100 Abbott Park Road, Abbott Park, IL 60064-6118, USA. steven.a.buckner@abbott.com

Abstract

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.

PMID:
10988346
DOI:
10.1016/s0014-2999(00)00388-5
[Indexed for MEDLINE]

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