A quantitative autoradiographical study on the distribution of somatostatin sst2 receptors in the rat central nervous system using [125I]-BIM-23027.
The kinetic properties, steady state binding characteristics and autoradiographic distribution of the somatostatin (SRIF) sst2 receptor-selective ligand, [125I]-BIM-23027, have been investigated in the rat central nervous system. Analysis of kinetic, saturation and competition binding data in rat hippocampal membranes was consistent with [125I]-BIM-23207 binding to a single population of non-interacting binding sites. Competition studies, using different SRIF ligands suggested that [125I]-BIM-23027 was binding to sites similar to that of the recombinant sst2 receptor. The rank order of affinity for displacing specific binding was BIM-23027 = SRIF > L-362855 > > BIM-23056. There was a widespread distribution of [125I]-BIM-23027 binding sites in the rat central nervous system. The highest density of binding was observed in the dentate gyrus, medial habenular, amygdala, claustrum and lateral septum as well as in the piriform, cingulate and parietal cortex. The cervical and lumbar spinal cord also displayed moderate levels of binding localized to the substantia gelatinosa. The cellular localization of [125I]-BIM-23027 binding was found to be associated with dendritic terminal fields. In contrast, the cellular signal for sst2 receptor mRNA was restricted to cell somata. The widespread distribution of [125I]-BIM-23027 binding sites within the brain suggests that receptors similar to the recombinant sst2 receptor may mediate a variety of different physiological effects within the central nervous system.
Holloway
S
S
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, U.K.
Feniuk
W
W
Kidd
E J
EJ
Humphrey
P P
PP
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D002490:Central Nervous System / Q000033:anatomy & histology / Q000378:metabolism*; D017403:In Situ Hybridization; D008024:Ligands; D008297:Male; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*
C091738:BIM 23027; D008024:Ligands; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D017481:Receptors, Somatostatin