Facilitation by 5-hydroxytryptamine of ATP-activated current in rat pheochromocytoma cells

Ken Nakazawa, Kaori Inoue, Shuichi Koizumi, Kazuhide Inoue

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The effects of 5-hydroxytryptamine (5-HT) on an inward current activated by extracellular ATP were investigated in rat pheochromocytoma PC12 cells. Under whole-cell voltage-clamp conditions 5-HT (10 μM) reversibly enhanced the amplitude of the current activated by 30 μM ATP. The enhancement may not be due to an increase in the number of functional channels because the current activated by 300 μM ATP was not remarkably augmented compared with the current activated by 30 μM ATP. The current enhancement by 100 μM 5-HT was less obvious than that by 10 μM 5-HT. When the current kinetics were compared, activation of the ATP-evoked current was accelerated to the same extent by either 10 or 100 μM 5-HT, whereas deactivation was largely more accelerated by 100 μM 5-HT. Propranolol (10 μM), a 5-HT1 receptor antagonist, or LY53857 (10 μM), a 5-HT2 receptor antagonist, exerted an agonistic effect: the ATP-activated current was facilitated by these compounds. Metoclopramide (10 μM), a 5-HT3 receptor antagonist, neither facilitated the ATP-activated current, nor blocked the current facilitation by 5-HT. Guanosine 5′-O-(2-thiodiphosphate) (GDP[βS]) (2 mM), the non-hydrolysable analog of guanosine 5′-triphosphate (GTP), or K-252a (2 μM), a protein kinase inhibitor, did not affect the facilitation by 5-HT of the ATP-activated current when they were included in the intracellular solution. The ATP-activated current pre-facilitated by 10 μM dopamine was not enhanced by 10 μM 5-HT. Similarly, the pre-facilitation by 5-HT attenuated the current enhancement by dopamine. The results suggest that 5-HT facilitates the ATP-activated channels through receptors that are not readily classified into conventional subclasses of 5-HT receptors. The reciprocal masking between the current facilitation by 5-HT and that by dopamine, combined with their sensitivities to the compounds involved in the intracellular solution, indicates that the facilitation by 5-HT may share not all, but some, common cellular mechanism with that by dopamine.

Original languageEnglish
Pages (from-to)492-499
Number of pages8
JournalPflügers Archiv European Journal of Physiology
Volume427
Issue number5-6
DOIs
Publication statusPublished - Jul 1 1994

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Pheochromocytoma
Rats
Serotonin
Adenosine Triphosphate
Dopamine
LY 53857
Serotonin 5-HT1 Receptors
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT3 Receptor Antagonists
Serotonin 5-HT2 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Metoclopramide
Guanosine
Serotonin Receptors
PC12 Cells
Clamping devices
Protein Kinase Inhibitors
Guanosine Triphosphate
Propranolol
Chemical activation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Facilitation by 5-hydroxytryptamine of ATP-activated current in rat pheochromocytoma cells. / Nakazawa, Ken; Inoue, Kaori; Koizumi, Shuichi; Inoue, Kazuhide.

In: Pflügers Archiv European Journal of Physiology, Vol. 427, No. 5-6, 01.07.1994, p. 492-499.

Research output: Contribution to journalArticle

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