PROSTACYCLIN RECEPTOR IN THE BRAIN AND CENTRAL TERMINALS OF THE PRIMARY SENSORY NEURONS - AN AUTORADIOGRAPHIC STUDY USING A STABLE PROSTACYCLIN ANALOG [H-3] ILOPROST

Presence and localization of the prostacyclin receptor in the rat brai n and spinal cord were examined by in vitro autoradiography using [H-3 ]iloprost, a highly specific and stable agonist for this receptor. Den sity of specific binding sites for iloprost was generally high in four regions of the lower brain stem, that is, the medial and commissural subnuclei of the nucleus tractus solitarius, the area postrema, superf icial layers of the spinal trigeminal nucleus caudalis and dorsal horn . Moderate density was found in the thalamus, cerebral cortex, hippoca mpus, striatum and dorsal cochlear nucleus. The distribution pattern w as distinct from those of other prostanoid binding sites previously st udied except that prostaglandin E(2) binding sites were also abundant in the nucleus tractus solitarius, spinal trigeminal nucleus caudalis and dorsal horn. Even in these regions, binding sites for iloprost had several features clearly different from those for prostaglandin E(2). First, within the medial and commissural subnuclei of the nucleus tra ctus solitarius, iloprost binding sites were distributed preferentiall y in the dorsal part, while those for prostaglandin E(2) were located more ventrolaterally. Second, on postnatal day 0, iloprost binding sit es have already been expressed in large amounts in the nucleus tractus solitarius, spinal trigeminal nucleus caudalis and dorsal horn of rat s, while prostaglandin E(2) binding sites are negligible at this stage . Thirdly, the binding of 10 nM [H-3]iloprost in these three regions w as almost completely displaced by 10 mu M unlabelled iloprost but only slightly by 10 mu M unlabelled prostaglandin E(2). Unilateral nodose ganglionectomy or dorsal rhizotomy decreased the density of iloprost b inding sites in the nucleus tractus solitarius or dorsal horn, respect ively, with a greater decrease in the operated side. Ligation of the v agus either central or peripheral to the nodose ganglion resulted in a n accumulation of iloprost binding sites proximal to the ligation. The se results suggest that specific binding sites for iloprost, presumabl y prostacyclin receptor, are present in the nervous system and, in par ticular, that the iloprost binding sites in the nucleus tractus solita rius, dorsal horn and possibly in the superficial layers of the spinal trigeminal nucleus caudalis are produced in their sensory ganglia and transported to central terminals of the primary sensory afferents as well as to their peripheral terminals.