Somatostatin activates two types of inwardly rectifying K+ channels in MIN-6 cells.
Western blotting revealed the presence of five somatostatin receptor types, sst1, sst2, sst3, sst4 and sst5, in the mouse pancreatic -cell line MIN-6. In MIN-6 cells, glucose-induced electrical activity was potently (pEC50 = 12.7) and irreversibly reduced by somatostatin (SRIF-14); this was associated with hyperpolarization of the membrane potential (pEC50 = 11.2) and a decrease in the input resistance (pEC50 = 12.7). The effects of SRIF-14 were mimicked by 100 nM L-362,855 (a partial agonist at sst5 receptors), but not BIM-23027 or NNC-26,9100 (selective agonists at sst2 and sst4 receptors, respectively). CH-275 at 100 nM (a selective agonist at sst1 receptors) partially inhibited electrical activity but without membrane potential hyperpolarization. One hundred nanomolar SRIF-28 activated an inwardly rectifying K+ current (ISRIF) ISRIF was activated neither by 1 M BIM-23056 nor CYN-154806 (antagonists at sst5 and sst2 receptors, respectively). The activation of ISRIF by 100 nM SRIF-28 was, however, inhibited 93 % by BIM-23056; CYN-154806 had no effect. Both 100 nM glibenclamide and 200 M tolbutamide, blockers of the -cell ATP-sensitive K+ channel (K-ATP), reduced ISRIF by ~44 %, whereas 1 mM Ba2+ abolished ISRIF. In cell-attached patches, 100 nM SRIF-14 activated two types of single-channel currents whose properties were consistent with those of K-ATP and GIRK channels. In conclusion, somatostatin can inhibit glucose-induced electrical activity in MIN-6 cells by the combined activation of K-ATP and GIRK channels. Studies with selective agonists and antagonists are consistent with this effect being mediated by the sst5 receptor.
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, UK. pas59404@glaxowellcome.co.uk
P A
PA
Smith
L A
LA
Sellers
P P
PP
Humphrey
D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology; D015151:Immunoblotting; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; D013004:Somatostatin; D005947:Glucose