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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 338, Issue 5, pp 560–566 | Cite as

Differential effects of potassium channel blockers on neurohypophysial release of oxytocin and vasopressin. Evidence for frequency-dependent interaction with the endogenous opioid inhibition of oxytocin release

  • K. Racké
  • U. Altes
  • A. M. Baur
  • H. P. Hobbach
  • D. Jost
  • J. Schäfer
  • R. Wammack
Article

Summary

Isolated rat neurohypophyses were fixed by their stalks to a platinum wire electrode and superfused with Krebs-HEPES solution. Vasopressin and oxytocin released into the medium were determined by specific radioimmunoassays. Hormone secretion was increased by electrical stimulation of the pituitary stalk at different frequencies. The effects of several potassium channel blockers, tetraethylammonium (TEA) ions, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) were tested.

The release of vasopressin and oxytocin evoked by electrical stimulation with 900 pulses at 15 Hz (about 900 and 1,000 μU, respectively) was about 10 times higher than that evoked by 900 pulses at 3 Hz. Both 10 and 30 mmol/l TEA enhanced the release of vasopressin evoked by stimulation at 3 and 15 Hz, by 25- and 2-fold, respectively, to attain a maximum release of about 1,800 μU per stimulation. The stimulated release of oxytocin attained a maximum of about 9,000 μU at 15 Hz in the presence of 10 mmol/l TEA or at 3 Hz with 30 mmol/l TEA. Thus, in the presence of maximally effective concentrations of TEA both stimulation frequencies (3 and 15 Hz) were equieffective in evoking release of vasopressin and oxytocin. 4-AP or 3,4-DAP enhanced the release of vasopressin evoked by 15 Hz stimulation maximally to about 1,600 μU and that evoked by 3 Hz stimulation to about 900 μU. In the presence of 4-AP or 3,4-DAP the release of oxytocin evoked by stimulation at 15 Hz increased maximally to about 8,000 μU and that evoked by stimulation at 3 Hz to about 1,500 μU. Thus, in the presence of maximally effective concentrations of 4-AP or 3,4-DAP stimulation at 15 Hz induced a significantly higher release of vasopressin and oxytocin than stimulation at 3 Hz. Naloxone (1 μmol/l) increased the release of oxytocin evoked by stimulation at 15 Hz to about 3,000 μU and that evoked by stimulation at 3 Hz to about 700 μU. The release of oxytocin evoked by stimulation at 15 Hz in the presence of 10 mmol/l TEA or 1 mmol/l 4-AP (about 8,000–9,000 μU) was not further enhanced by naloxone. However, during stimulation at 1 or 3 Hz in the presence of 10 mmol/l TEA, naloxone increased the release of oxytocin from about 3,700 and 6,300 μU, respectively, to the maximum of about 9,000 μU. Likewise, during stimulation at 3 Hz in the presence of 1 mmol/14-AP, naloxone increased the relase of oxytocin from about 1,500 to 9,000 μU. Under all condition studied, naloxone did not affect the release of vasopressin.

In conclusion, neurosecretory nerve endings are endowed with different types of potassium channels. Blockade of potassium channels can oppose the opioid inhibition of oxytocin release in a complex frequency-dependent manner.

Key words

Vasopressin release Oxytocin release Neurohypophysis Potassium channels Stimulus secretion coupling Tetraethylammonium ions Aminopyridines 

Abbreviations

4-AP

4-aminopyridine

3,4-DAP

3,4-diaminopyridine

TEA

tetraethylammonium ions

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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • K. Racké
    • 1
  • U. Altes
    • 1
  • A. M. Baur
    • 1
  • H. P. Hobbach
    • 1
  • D. Jost
    • 1
  • J. Schäfer
    • 1
  • R. Wammack
    • 1
  1. 1.Pharmakologisches Institut der Universität MainzMainzGermany

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