Specific inhibition of Ca-activated K channels in red cells by selected dihydropyridine derivatives.
1. Thirty two dihydropyridine derivatives were screened as potential inhibitors of the Ca-activated K-channel in human red cells. 2. Three derivatives (26, 29, 32 see Tables 1 and 2) with high activity were then characterized in detail, and also tested against the smooth muscle Ca-channel and shown to have varying potencies. 3. One of the more potent derivatives (32) and nitrendipine were also tested on the Ca-activated K-channel, Maxi-K channel, from mouse pancreatic beta-cells. 4. We conclude from our results that it may be possible to develop selective Gardos-channel inhibitors based on these molecules, which may be of benefit in the treatment of sickle cell disease.
Department of Physiology, University of Oxford.
J C
JC
Ellory
S J
SJ
Culliford
P A
PA
Smith
M W
MW
Wolowyk
E E
EE
Knaus
D002118:Calcium / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004912:Erythrocytes / Q000737:chemistry*; D006801:Humans; D009568:Nitrendipine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000097:blood* / Q000187:drug effects
D004095:Dihydropyridines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009568:Nitrendipine; D002118:Calcium