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 pit uitary tumor cells (White et al., Nature, 351, 570-573, 1991) is block ed by drugs that interfere with arachidonic acid release by phospholip ase A(2) and metabolism by 5-lipoxygenase. In contrast, higher concent rations of the same drugs had no effect on BK channel gating in cell-f ree patches, on the inhibition of adenylyl cyclase by somatostatin, or on the stimulation of BK channels by protein dephosphorylation throug h a cGMP-dependent pathway (White et al., Nature 361, 263-266, 1993). Exogenous arachidonic acid (1-20 mu M) stimulated BK channel activity through protein dephosphorylation as effectively as somatostatin and w as also blocked by inhibitors of lipoxygenases but not by inhibitors o f phospholipase A(2) These results support the hypothesis that lipoxyg enase metabolites of arachidonic acid are second messengers linking pe rtussis toxin sensitive G-proteins to protein phosphatases regulating potassium channel activity (Armstrong and White, Trends Neurosci. 15, 403-408, 1992).