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.
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, tetraethyl-ammonium (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 microU, 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 microU per stimulation. The stimulated release of oxytocin attained a maximum of about 9,000 microU 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 microU. 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 microU and that evoked by stimulation at 3 Hz to about 1,500 microU.(ABSTRACT TRUNCATED AT 250 WORDS)
Racké
K
K
Pharmakologisches Institut der Universität Mainz, Federal Republic of Germany.
Altes
U
U
Baur
A M
AM
Hobbach
H P
HP
Jost
D
D
Schäfer
J
J
Wammack
R
R
D015761:4-Aminopyridine; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004558:Electric Stimulation; D004723:Endorphins / Q000502:physiology; D005260:Female; D009270:Naloxone / Q000494:pharmacology; D010121:Oxytocin / Q000032:analysis / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D014667:Vasopressins / Q000032:analysis / Q000378:metabolism*
D000631:Aminopyridines; D001578:Benzopyrans; D004723:Endorphins; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D014667:Vasopressins; D009270:Naloxone; D010121:Oxytocin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D000077770:Amifampridine