title: Actions of prostaglandin E2 on rat supraoptic neurones.
abstract: Prostaglandins (PGs) have been implicated in the regulation of vasopressin (VP) and oxytocin (OT) release in response to various stimuli. To examine the site and mechanism of actions of PGs, we studied effects of PGE2 and PG-receptor agonists on supraoptic nucleus (SON) neurones of rat hypothalamic slice preparations using extracellular recording and whole-cell patch-clamp techniques. PGE2 modulated the electrical activity of more than 80% of the neurones studied. The effects of PGE2 on both phasic and non-phasic neurones were mostly excitatory, and dose-dependent. The effects of PGE2 were mimicked by PGF2alpha or the FP agonist, fluprostenol, whereas PGD2 or the selective EP, IP or TP agonist was less effective or had no effect. The effects of PGE2 were unaffected by the EP1 antagonist, SC-51322, but reduced to 80% of control by the EP1/FP/TP antagonist, ONO-NT-012, which reduced the effects of fluprostenol to 32% of control. Moreover, some neurones responsive to PGE2 did not respond to fluprostenol. Patch-clamp analysis in SON slice preparations revealed that PGE2 at 10(-6) M depolarized the membrane potential by 3.9+/-0.3 mV from the resting membrane potential of -58.4+/-2.2 mV in the current-clamp mode. In the voltage-clamp mode, PGE2 induced inward currents at a holding potential of -70 or -80 mV, while it did not affect spontaneous excitatory postsynaptic currents. PGE2 induced currents also in dissociated SON neurones and the reversal potential of the currents was -35.5+/-0.9 mV, which was similar to that of currents induced by fluprostenol. These results suggest that SON neurones possess at least two types of PG receptors, FP receptors and EP receptors of a subclass different from EP1, EP2, or EP3, and that activation of these receptors leads to the opening of nonselective cation channels, membrane depolarization and increase of the action potential discharge.
authors.affiliation: Department of Physiology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: V
authors.initials: V
authors.lastname: Sutarmo Setiadji
authors.forename: I
authors.initials: I
authors.lastname: Shibuya
authors.forename: N
authors.initials: N
authors.lastname: Kabashima
authors.forename: N
authors.initials: N
authors.lastname: Ibrahim
authors.forename: N
authors.initials: N
authors.lastname: Harayama
authors.forename: Y
authors.initials: Y
authors.lastname: Ueta
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010077:Oxazepines / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015230:Prostaglandin D2 / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors; D013343:Styrenes / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology* / Q000187:drug effects
chemical_list: C092396:17-phenyltrinorprostaglandin E2; D001643:Bridged Bicyclo Compounds; C095324:ONO-NT 012; D010077:Oxazepines; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; D013343:Styrenes; C016767:sulprostone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2