Dopamine D 2 ‐like receptor‐mediated opening of K + channels in opossum kidney cells

This study examined the effects of dopamine D 1 ‐ and D 2 ‐like receptor activation upon basolateral K + ( I K ) currents and changes in membrane potential in opossum kidney (OK) cells. The addition of amphotericin B (3 μg ml −1 ) to the apical side resulted in a rapid increase in I K , this effect being markedly inhibited by the addition of the K + channel blockers barium chloride (1 m M ) or glibenclamide (10 μ M ), but not apamin (1 μ M ). The K + channel opener pinacidil increased the amphotericin B‐induced I K . The selective D 2 ‐like receptor agonist quinerolane increased, in a concentration dependent manner (EC 50 =136 n M ), I K across the basolateral membrane, this effect being abolished by pre‐treatment with pertussis toxin (PTX), S‐sulpiride (selective D 2 ‐like receptor antagonist) and glibenclamide. The selective D 1 ‐like receptor agonist SKF 38393 did not change I K . Both H‐89 (PKA inhibitor) and chelerythrine (PKC inhibitor) failed to prevent the stimulatory effect of quinerolane upon I K . Quinerolane did not change basal levels of cyclic AMP and also failed to affect the forskolin‐induced increase in cyclic AMP levels. The stimulation of D 2 ‐like receptor was associated with a rapid hyperpolarizing effect, whereas D 1 ‐like receptor activation was accompanied by increases in cell membrane potential. The hyperpolarizing effect of quinerolane (EC 50 =129 n M ) was prevented by pre‐treatment with PTX, S‐sulpiride and glibenclamide. It is concluded that stimulation of dopamine D 2 ‐like, but not D 1 ‐like, receptors coupled to PTX‐sensitive G proteins of the G i/o class produce membrane hyperpolarization through opening of K ATP channels.British Journal of Pharmacology (2003) 138 , 968–976. doi: 10.1038/sj.bjp.0705125