Dopamine D2-like receptor-mediated opening of K+ channels in opossum kidney cells.
(1) 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. (2) The addition of amphotericin B (3 micro g 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 mM) or glibenclamide (10 micro M), but not apamin (1 micro 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 nM), 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). (3) Quinerolane did not change basal levels of cyclic AMP and also failed to affect the forskolin-induced increase in cyclic AMP levels. (4) 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 nM) was prevented by pre-treatment with PTX, S-sulpiride and glibenclamide. (5) 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.
Gomes
Pedro
P
Institute of Pharmacology & Therapeutics, Faculty of Medicine, 4200 Porto, Portugal.
Soares-da-Silva
Patrício
P
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009893:Opossums / Q000502:physiology*; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*
D015221:Potassium Channels; D017448:Receptors, Dopamine D2