Active relaxation of human gallbladder muscle is mediated by ATP-sensitive potassium channels.
BACKGROUND
Active and significant relaxation of the human gallbladder must be one of the facets of its motility during both the filling and emptying cycle. Conflicting reports about the presence or significance of nitric oxide have been reported in the literature. The aim of this study was to investigate the role of nitric oxide and K(ATP) channels in human gallbladder muscle using isolated strips from human gallbladder.


METHODS
Full thickness strips were obtained from 56 human gallbladders and suspended under isometric tension in organ baths. The effect of nitric oxide donors and inhibitors on cholecystokinin octapeptide- and carbachol-induced contraction was examined. In separate experiments the effect of the K(ATP) channel activator, cromakalim, and the inhibitor, glibenclamide, were determined.


RESULTS
Cromakalim induced a significant relaxation of agonist-induced contraction in human gallbladder in vitro, an effect which was abolished by the K(ATP) channel inhibitor glibenclamide. No evidence of significant nitric oxide involvement in relaxation was observed.


CONCLUSIONS
This study has demonstrated the presence of K(ATP) channels in human gallbladder for the first time. These are capable of causing significant relaxation in the presence of hormonal and muscarinic agonists and may represent a major pathway for gallbladder relaxation.
Bird
N C
NC
Academic Surgical Unit, Royal Hallamshire Hospital, University of Sheffield, UK. n.bird@shef.ac.uk
Ahmed
R
R
Chess-Williams
R
R
Johnson
A G
AG
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D005704:Gallbladder / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D015221:Potassium Channels; D019806:Cromakalim; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002217:Carbachol; D012844:Sincalide; D005905:Glyburide