Actions of prostaglandin E-2 on rat supraoptic neurones

Prostaglandins (PGs) have been implicated in the regulation of vasopressin (VP) and oxytocin (OT) release in response to various stimuli, To examine t he site and mechanism of actions of PGs, we studied effects of PGE(2) and P G-receptor agonists on supraoptic nucleus (SON) neurones of rat hypothalami c slice preparations using extracellular recording and whole-cell patch-cla mp techniques. PGE(2) modulated the electrical activity of more than 80% of the neurones studied. The effects of PGE(2) on both phasic and non-phasic neurones were mostly excitatory, and dose-dependent. The effects of PGE(2) were mimicked by PGF(2 alpha) or the FP agonist, fluprostenol, whereas PGD( 2) or the selective EP, IP or TP agonist was less effective or had no effec t. The effects of PGE(2) were unaffected by the EP1 antagonist, SC-51322, b ut 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 neur ones responsive to PGE(2) did not respond to fluprostenol. Patch-clamp anal ysis in SON slice preparations revealed that PGE(2) at 10(-6) M depolarized the membrane potential by 3.9 +/- 0.3 mV from the resting membrane potenti al of -58.4 +/- 2.2 mV in the current-clamp mode. In the voltage-clamp mode , PGE(2) induced inward currents at a holding potential of -70 or - 80 mV, while it did not affect spontaneous excitatory postsynaptic currents. PGE(2 ) induced currents also in dissociated SON neurones and the reversal potent ial of the currents was -35.5+/-0.9 mV, which was similar to that of curren ts induced by fluprostenol, These results suggest that SON neurones possess at least two types of PG receptors, FP receptors and EP receptors of a sub class different from EP1, EP2, or EP3, and that activation of these recepto rs leads to the opening of nonselective cation channels, membrane depolariz ation and increase of the action potential discharge.