title: Somatostatin stimulates Ca(2+)-activated K+ channels through protein dephosphorylation.
abstract: The neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain. In mammalian pituitary tumour cells somatostatin inhibits secretion through two distinct pertussis toxin-sensitive mechanisms. One involves inhibition of adenylyl cyclase, the other an unidentified cyclic AMP-independent mechanism that reduces Ca2+ influx by increasing membrane conductance to potassium. Here we demonstrate that the predominant electrophysiological effect of somatostatin on metabolically intact pituitary tumour cells is a large, sustained increase in the activity of the large-conductance Ca(2+)- and voltage-activated K+ channels (BK). This action of somatostatin does not involve direct effects of Ca2+, cAMP or G proteins on the channels. Our results indicate instead that somatostatin stimulates BK channel activity through protein dephosphorylation.
authors.affiliation: Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: R E
authors.initials: RE
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Schonbrunn
authors.forename: D L
authors.initials: DL
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D018999:Charybdotoxin; D000242:Cyclic AMP / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology; D066298:In Vitro Techniques; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010902:Pituitary Gland / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology; D013004:Somatostatin / Q000502:physiology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004988:Ethers, Cyclic; D010750:Phosphoproteins; D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D019319:Okadaic Acid; D013004:Somatostatin; D000242:Cyclic AMP; D010749:Phosphoprotein Phosphatases; D002118:Calcium