K(ATP) channels mediate the beta(2)-adrenoceptor agonist-induced relaxation of rat detrusor muscle.
We propose that ATP-sensitive K(+) (K(ATP)) channels are normally inactive but involved in beta(2)-adrenoceptor stimulated relaxation of the rat bladder. Spontaneous detrusor muscle contractions were unaffected by glibenclamide (K(ATP) channel blocker) but were reduced when pinacidil (K(ATP) channel opener) concentrations exceeded 10(-5) M. Inhibition by beta(2)-adrenoceptor agonist clenbuterol [10(-6) M] of 1 Hz electrical field stimulated contractions was abolished by glibenclamide [10(-6) M]. Glibenclamide [10(-6) M] decreased forskolin-induced relaxation [10(-9)-10(-4) M] in bladder muscle stimulated with 1 Hz electrical field. In the presence glibenclamide (10(-6) M) or myristoylated protein kinase A inhibitor (2)x[10(-6) M], clenbuterol [10(-9)-10(-5) M] failed to inhibit bladder contraction in response to 1 Hz electrical field stimulation. Therefore, K(ATP) channel opening and the subsequent hyperpolarization of cell membranes in response to beta(2)-adrenoceptor activation is mediated by raised cyclic-AMP levels and activation of protein kinase A. This counteracts ATP-stimulated depolarization in bladder muscle, thereby reducing cell contraction.
Hudman
D
D
Department of Medicine, Division of Medicine for the Elderly, University of Leicester, Leicester General Hospital, LE5 4PW, Leicester, UK. dh35@le.ac.uk
Elliott
R A
RA
Norman
R I
RI
D000255:Adenosine Triphosphate / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015221:Potassium Channels; D014665:Vasodilator Agents; D005576:Colforsin; D020110:Pinacidil; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005905:Glyburide; D002976:Clenbuterol