A novel subtype of prostacyclin receptor in the central nervous system

Recently, in the course of our search for the prostacyclin receptor in the brain, we found a novel subtype, designated as IP2, which was finely discri minated by use of the specific ligand (15R)-16-m-tolyl-17,18,19,20-tetranor isocarbacyclin (15R-TIC) and specifically localized in the rostral part of the brain. In the present study, the tritiated compound 15R-[15-H-3]TIC was synthesized and utilized for more specific research on IP2. The specificit y of binding to rat brain regions was confirmed by use of several prostacyc lin derivatives including 15S-TIC. Mapping of 15R- and 15S-[H-3]TIC binding in adjacent pairs of frozen sections of rat brain demonstrated a quite sim ilar pattern of distribution in almost all rostral brain regions, indicatin g that the regions may contain only the IP(2)subtype. On the other hand, 15 R-[3H]TIC binding was very faint as compared with 15S-[3H]TIC binding in th e caudal medullary region. High densities of 15R-[3H]TIC binding sites were shown in the dorsal part of the lateral septal nucleus, thalamic nuclei, l imbic structures, and some of the cortical regions. Scatchard plot analysis showed two components of high-affinity 15R-[3H]TIC binding in the rostral regions, one with a K-D value at similar to 1 nM and the other with similar to 30 nM, These results strengthen our previous finding that a different s ubtype of prostacyclin receptor is expressed in the CNS, and the map with 1 5R-[H-3]TIC obtained here could guide further studies on the molecular and functional properties of the IP2.