Somatostatin peptides inhibit basolateral potassium channels in human colonic crypts.
Somatostatin is a powerful inhibitor of intestinal Cl(-) secretion. We used patch-clamp recording techniques to investigate the effects of somatostatin on low-conductance (23-pS) K(+) channels in the basolateral membrane of human colonic crypts, which are an important component of the Cl(-) secretory process. Somatostatin (2 microM) elicited a >80% decrease in "spontaneous" K(+) channel activity in cell-attached patches in nonstimulated crypts (50% inhibition = approximately 8 min), which was voltage-independent and was prevented by pretreating crypts for 18 h with pertussis toxin (200 ng/ml), implicating a G protein-dependent mechanism. In crypts stimulated with 100-200 microM dibutyryl cAMP, 2 microM somatostatin and its synthetic analog octreotide (2 microM) both produced similar degrees of K(+) channel inhibition to that seen in nonstimulated crypts, which was also present under low-Cl(-) (5 mM) conditions. In addition, 2 microM somatostatin abolished the increase in K(+) channel activity stimulated by 2 microM thapsigargin but had no effect on the thapsigargin-stimulated rise in intracellular Ca(2+). These results indicate that somatostatin peptides inhibit 23-pS basolateral K(+) channels in human colonic crypt cells via a G protein-dependent mechanism, which may result in loss of the channel's inherent Ca(2+) sensitivity.
Sandle
G I
GI
Molecular Medicine Unit, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, United Kingdom. g.i.sandle@leeds.ac.uk
Warhurst
G
G
Butterfield
I
I
Higgs
N B
NB
Lomax
R B
RB
D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002712:Chlorides; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D003994:Bucladesine; D019284:Thapsigargin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium