Abstract
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 μM) augmented the peak amplitude of an inward current elicited by ATP (3-100 μM). The activation time course of the ATP-evoked current was accelerated by dopamine; the presence of 10 μM 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 μM), 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 γS (1 mM) or α-β-methylene ATP (1 mM). Inclusion of adenosine 3′, 5′-cyclic monophosphate sodium salt (cAMP, 100 μM), guanosine 3′,5′-cyclic monophosphate sodium salt (cGMP, 100 μM), 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 μM) or phorbol-12,13-dibutylate (1 μM) in the intracellular solution did not affect the facilitation. Guanonsine 5′-O-(thiotriphosphate)tetralithium salt (GTP γS, 500 μM) or guanosine 5′-O(2-thiodiphosphate)-trilithium salt (GDP βS, 500 μM) did not modify the facilitation either. The results suggest that dopamine augments the ATP-activated inward current by facilitating association of ATP to its binding site, and that the augmentation may be mediated through some protein kinase which is different from cyclic-nucleotide-dependent protein kinases or protein kinase C.
| Original language | English |
|---|---|
| Pages (from-to) | 458-464 |
| Number of pages | 7 |
| Journal | Pflügers Archiv European Journal of Physiology |
| Volume | 422 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Feb 1 1993 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Physiology
- Clinical Biochemistry
- Physiology (medical)
Cite this
Mechanisms underlying facilitation by dopamine of ATP-activated currents in rat pheochromocytoma cells. / Nakazawa, Ken; Watano, Tomokazu; Inoue, Kazuhide.
In: Pflügers Archiv European Journal of Physiology, Vol. 422, No. 5, 01.02.1993, p. 458-464.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mechanisms underlying facilitation by dopamine of ATP-activated currents in rat pheochromocytoma cells
AU - Nakazawa, Ken
AU - Watano, Tomokazu
AU - Inoue, Kazuhide
PY - 1993/2/1
Y1 - 1993/2/1
N2 - 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 μM) augmented the peak amplitude of an inward current elicited by ATP (3-100 μM). The activation time course of the ATP-evoked current was accelerated by dopamine; the presence of 10 μM 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 μM), 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 γS (1 mM) or α-β-methylene ATP (1 mM). Inclusion of adenosine 3′, 5′-cyclic monophosphate sodium salt (cAMP, 100 μM), guanosine 3′,5′-cyclic monophosphate sodium salt (cGMP, 100 μM), 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 μM) or phorbol-12,13-dibutylate (1 μM) in the intracellular solution did not affect the facilitation. Guanonsine 5′-O-(thiotriphosphate)tetralithium salt (GTP γS, 500 μM) or guanosine 5′-O(2-thiodiphosphate)-trilithium salt (GDP βS, 500 μM) did not modify the facilitation either. The results suggest that dopamine augments the ATP-activated inward current by facilitating association of ATP to its binding site, and that the augmentation may be mediated through some protein kinase which is different from cyclic-nucleotide-dependent protein kinases or protein kinase C.
AB - 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 μM) augmented the peak amplitude of an inward current elicited by ATP (3-100 μM). The activation time course of the ATP-evoked current was accelerated by dopamine; the presence of 10 μM 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 μM), 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 γS (1 mM) or α-β-methylene ATP (1 mM). Inclusion of adenosine 3′, 5′-cyclic monophosphate sodium salt (cAMP, 100 μM), guanosine 3′,5′-cyclic monophosphate sodium salt (cGMP, 100 μM), 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 μM) or phorbol-12,13-dibutylate (1 μM) in the intracellular solution did not affect the facilitation. Guanonsine 5′-O-(thiotriphosphate)tetralithium salt (GTP γS, 500 μM) or guanosine 5′-O(2-thiodiphosphate)-trilithium salt (GDP βS, 500 μM) did not modify the facilitation either. The results suggest that dopamine augments the ATP-activated inward current by facilitating association of ATP to its binding site, and that the augmentation may be mediated through some protein kinase which is different from cyclic-nucleotide-dependent protein kinases or protein kinase C.
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U2 - 10.1007/BF00375072
DO - 10.1007/BF00375072
M3 - Article
C2 - 7682686
AN - SCOPUS:0027499173
VL - 422
SP - 458
EP - 464
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
SN - 0031-6768
IS - 5
ER -