Mechanisms underlying facilitation by dopamine of ATP-activated currents in rat pheochromocytoma cells.
Mechanisms underlying facilitation by dopamine of extracellular adenosine 5'-triphosphate (ATP)-activated current were investigated in rat pheochromocytoma PC12 cells using the whole-cell voltage-clamp techniques. Dopamine (10 and 100 microM) augmented the peak amplitude of an inward current elicited by ATP (3-100 microM). The activation time course of the ATP-evoked current was accelerated by dopamine; the presence of 10 microM dopamine shifted the dependence of activation rate constants on the concentration of ATP toward a lower concentration range two fold. Dopamine also accelerated the inactivation and the deactivation, which was determined from the current decay upon washout of ATP. Intracellular mediators responsible for the dopamine-induced facilitation was estimated by loading various compounds in patch pipettes. Facilitation was not observed when K-252a (1 microM), a protein kinase inhibitor, was included in the intracellular solution. In addition, facilitation was also attenuated by intracellular adenosine 5'-O-(thiotriphosphate)tetralithium salt (ATP gamma S (1 mM) or alpha-beta-methylene ATP (1 mM). Inclusion of adenosine 3',5'-cyclic monophosphate sodium salt (cAMP, 100 microM), guanosine 3',5'-cyclic monophosphate sodium salt (cGMP, 100 microM), 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microM) or phorbol-12,13-dibutyrate (1 microM) in the intracellular solution did not affect the facilitation. Guanosine 5'-O-(thiotriphosphate)tetralithium salt (GTP gamma S, 500 microM) or guanosine 5'-O(2-thiodiphosphate)-trilithium salt (GDP beta S, 500 microM) did not modify the facilitation either.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Watano
T
T
Inoue
K
K
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D016716:PC12 Cells; D047428:Protein Kinase Inhibitors; D051381:Rats
D007473:Ion Channels; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D004298:Dopamine