Somatostatin stimulates BKCa channels in rat pituitary tumor cells through lipoxygenase metabolites of arachidonic acid.
The stimulation of large-conductance, calcium-activated (BK) potassium channels by somatostatin through protein dephosphorylation in rat pituitary tumor cells (White et al., Nature 351, 570-573, 1991) is blocked by drugs that interfere with arachidonic acid release by phospholipase A2 and metabolism by 5-lip-oxygenase. In contrast, higher concentrations of the same drugs had no effect on BK channel gating in cell-free patches, on the inhibition of adenylyl cyclase by somatostatin, or on the stimulation of BK channels by protein dephosphorylation through a cGMP-dependent pathway (White et al., Nature 361, 263-266, 1993). Exogenous arachidonic acid (1-20 muM) stimulated BK channel activity through protein dephosphorylation as effectively as somatostatin and was also blocked by inhibitors of lipoxygenases but not by inhibitors of phospholipase A2. These results support the hypothesis that lipoxygenase metabolites of arachidonic acid are second messengers linking pertussis toxin sensitive G-proteins to protein phosphatases regulating potassium channel activity (Armstrong and White, Trends Neurosci. 15, 403-408, 1992).
Duerson
K
K
Laboratory of Cellular & Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
White
R E
RE
Jiang
F
F
Schonbrunn
A
A
Armstrong
D L
DL
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010911:Pituitary Neoplasms / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D051036:Large-Conductance Calcium-Activated Potassium Channels; D016859:Lipoxygenase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D013757:Tetraethylammonium Compounds; D016718:Arachidonic Acid; D013004:Somatostatin; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054467:Phospholipases A2