Prostaglandin E2 modulates a non-inactivating potassium current in rat neurohypophyseal nerve terminals.
A non-inactivating voltage dependent K+ channel current was observed in neuro-hypophyseal nerve terminals. This current was sensitive to inhibition by 4-aminopyridine and tetraethyl ammonium chloride, but was not sensitive to inhibition by alpha- or beta-dendrotoxin. Prostaglandin E2 (PGE2) modulated the voltage-dependent K+ channel, through a receptor-mediated process, as indicated by meclofenamate sensitivity, and this involved the activation of G protein(s), as indicated by sensitivity to guanosine-5'-O-(2-thiodiphosphate) (GDPfS). After short periods of incubation (e.g. 5 min), PGE2 increased the non-inactivating current. Following longer incubation periods with PGE2 (e.g. 20 min), the non-inactivating current declined. Forskolin and the cyclic adenosine monophosphate (AMP) analogs 8-bromo- and dibutyryl cyclic AMP, and Sp-cyclic AMPs inhibited the current, but did not mimic the increase in current caused by PGE2. Also, the cyclic AMP antagonist Rp-cyclic AMPs did not block the increase in current induced by PGE2. These results indicate that activation of cyclic AMP-dependent protein kinase (PKA) is not involved in mediating the stimulatory actions of PGE2. These observations provide evidence that PGE2 may contribute to the regulation of hormone release from the posterior pituitary by modulating K+ channels. However, the post-receptor mechanisms of subcellular signal transduction underlying this effect remain unknown.
Zhang
L
L
Department of Physiology, University of Alberta, Edmonton, Canada.
Karpinski
E
E
Benishin
C G
CG
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects* / Q000502:physiology; D010904:Pituitary Gland, Posterior / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000502:physiology; D013873:Thionucleotides / Q000502:physiology
D015221:Potassium Channels; D018078:Receptors, Prostaglandin E; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D000242:Cyclic AMP; D015232:Dinoprostone