Prostaglandin E-2 inhibits spontaneous inhibitory postsynaptic currents inrat supraoptic neurones via presynaptic EP receptors

Prostaglandin E-2 (PGE(2)) has been implicated in the excitatory regulation of magnocellular neurones in the supraoptic nucleus (SON). We have recentl y reported that PGE(2) excited SON neurones by directly activating postsyna ptic PGE(2) receptors (EP receptors) of a subclass other than EP1-3, but di d not affect excitatory postsynaptic currents (EPSCs), In the present study , we examined presynaptic effects of PGE(2) on rat SON neurones by measurin g spontaneous inhibitory postsynaptic currents (IPSCs) by a slice patch-cla mp technique. PGE(2) inhibited spontaneous IPSCs in a dose-dependent and re versible manner. PGE(2) selectively suppressed the frequency of IPSCs witho ut affecting the amplitude of IPSCs in the presence of tetrodotoxin, a bloc ker of Na+ channels, indicating that the effects were presynaptic. The inhi bitory effects of PGE(2) on the frequency of IPSCs were mimicked by the EP1 /EP3 agonists, 17PT-PGE(2) and sulprostone, and the EP2/EP3 agonist, misopr ostol, whereas the EP2 agonist, butaprost, or the FP agonist, fluprostenol, had little effect. The effects of PGE(2) on IPSCs were unaffected by the s elective EP1 antagonist, SC-51322, They were unaffected also by antagonists of GABA(B) and alpha(2) adrenergic receptors, which are present at presyna ptic terminals of GABA neurones in the SON and cause suppression of spontan eous IPSCs, The inhibitor of PG synthesis, indomethacin, had little effect on spontaneous IPSCs and on the inhibitory effects of PGE(2) as well as of the GABA(B) agonist, baclofen, and noradrenaline. These results suggest tha t PGE(2) inhibits release of GABA from the GABAergic terminals innervating SON neurones by activating presynaptic EP receptors, presumably of the EP3 subclass, and that such a presynaptic mechanism may play a role in the exci tatory regulation of SON neurones by PGE(2).