A NOVEL SUBTYPE OF THE PROSTACYCLIN RECEPTOR EXPRESSED IN THE CENTRAL-NERVOUS-SYSTEM

By use of several prostacyclin analogs and an in vitro autoradiographi c technique, we have found a novel subtype of the prostacyclin recepto r, one having different binding properties compared with those of the known prostacyclin receptor in the rat brain. Isocarbacyclin, which is a potent agonist for the known prostacyclin receptor, had high affini ty for the novel subtype (dissociation constant (H-d) of 7.8 nM). Howe ver, iloprost, which is usually used as a stable prostacyclin analog, showed low affinity binding (K-d = 159 nM) for the subtype. Other pros taglandins showed no or little affinity for the subtype. [H-3]Isocarba cyclin binding was high in the thalamus, lateral septal nucleus, hippo campus, cerebral cortex, striatum, and dorsal cochlear nucleus. Althou gh the nucleus of the solitary tract and the spinal trigeminal nucleus showed a high density of [H-3]isocarbacyclin binding, [H-3]iloprost a lso had high affinity in these regions, and the binding specificity wa s similar to that for the known prostacyclin receptor. Hemilesion stud ies of striatal neurons lesioned by kainate or of dopaminergic afferen ts lesioned by 6-hydroxydopamine revealed that the binding sites of th e novel subtype exist on neuronal cells in the striatum, but not on th e presynaptic terminal of afferents or on glial cells. Electrophysiolo gical studies carried out in the CA1 region of the hippocampus reveale d that prostacyclin analogs have a facilitatory effect on the excitato ry transmission through the novel prostacyclin receptor. The widesprea d expression of the prostacyclin receptor in the central nervous syste m suggests that prostacyclin has important roles in neuronal activity.