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Journal of Pharmacology and Experimental Therapeutics

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OtherNEUROPHARMACOLOGY

Dopamine D4 Receptor Mediated Inhibition of Potassium Current in Neurohypophysial Nerve Terminals

Russell A. Wilke, Shyue-Fang Hsu and Meyer B. Jackson
Journal of Pharmacology and Experimental Therapeutics February 1998, 284 (2) 542-548;
Russell A. Wilke
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Shyue-Fang Hsu
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Meyer B. Jackson
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Abstract

Dopamine influences the release of neurohypophysial peptides in vivo. However, the extent to which this effect is caused by a direct dopaminergic action within the neurohypophysis remains unclear. With use of the patch-clamp technique on thin slices of rat posterior pituitary glands, we now provide evidence that dopaminergic agonists inhibit potassium current (IK) in neurohypophysial nerve terminals. Superfusion with the dopamine receptor agonist, (±)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin (PPHT), causes a reversible inhibition of whole-terminal IKunder voltage clamp. This effect is concentration-dependent, with a maximal inhibition of 40 ± 5% and an EC50 of 1.8 ± 1.0 μM. It can be blocked with either a nonselective D2-like antagonist (100 μM eticlopride) or with the highly selective D4 antagonist, RBI-257 (10 μM). U101958 (a derivative of RBI-257) exhibits agonist activity similar to PPHT. Neither SKF 38393 (a D1/D5 agonist) nor quinpirole (a D2/D3 agonist) had any effect on whole-terminal IK in this preparation. Kinetic analysis demonstrated that the amplitude of both the rapidly and slowly inactivating phases of neurohypophysialIK are reduced by D4 receptor activation. These two separate current components have previously been shown to represent current through two distinct potassium channels, an A-current channel and a high-conductance Ca++-activated K+ channel. Thus, both channel types can be modulated by D4 receptors. This effect is likely to enhance the release of neurohypophysial peptides in vivo.

Footnotes

  • Send reprint requests to: Meyer B. Jackson, PhD, Department of Physiology, 121 Service Memorial Institute, University of Wisconsin School of Medicine, 1300 University Avenue, Madison, WI 53706.

  • ↵1 Support for this research was provided by National Institutes of Health grant NS30016.

  • ↵2 Trainee in the Clinical Investigator Pathway and a postdoctoral fellow in the Department of Physiology at the University of Wisconsin.

  • Abbreviations:
    aCSF
    artificial cerebrospinal fluid
    ADH
    antidiuretic hormone
    IK
    potassium current
    OXT
    oxytocin
    PPHT
    (±)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin
    • Received May 13, 1997.
    • Accepted October 27, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 2
1 Feb 1998
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OtherNEUROPHARMACOLOGY

Dopamine D4 Receptor Mediated Inhibition of Potassium Current in Neurohypophysial Nerve Terminals

Russell A. Wilke, Shyue-Fang Hsu and Meyer B. Jackson
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 542-548;

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OtherNEUROPHARMACOLOGY

Dopamine D4 Receptor Mediated Inhibition of Potassium Current in Neurohypophysial Nerve Terminals

Russell A. Wilke, Shyue-Fang Hsu and Meyer B. Jackson
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 542-548;
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