title: Autoradiographic analysis of somatostatin SRIF1 and SRIF2 receptors in the human brain and pituitary.
abstract: The distribution of somatostatin (SRIF) receptor sites was studied by in vitro receptor autoradiography in the human brain and pituitary using the SRIF1 (sst2) receptor selective [125I]Tyr3-octreotide, the non-subtype selective [125I]LTT-SRIF-28 ([Leu8,D-Trp22, 125I-Tyr25]SRIF-28) and the SRIF2-receptor selective [125I]CGP 23996 (c[Asu- Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) in buffer containing 120 mM Na+. SRIF receptor autoradiography was compared with mRNA expression of somatostatin receptors sst1-5 as studied by in situ hybridisation in human brain. High levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide recognition sites were found in the deep layers of cerebral cortex and molecular layer of cerebellum of the human brain. The hypothalamus, choroid plexus, most areas of the brainstem and dentate nucleus were associated with low levels of binding. In contrast to [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide, no difference was observed for [125I]CGP 23996 labelling in the various layers of cerebral cortex. The choroid plexus, substantia nigra and molecular layer of the cerebellum presented high densities of [125I]CGP 23996 binding sites whereas no binding was observed in the hypothalamus and locus coeruleus using this radioligand. Both lobes of the human pituitary displayed low levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide binding. By contrast, the anterior lobe of the pituitary displayed very high levels of [125I]CGP 23996 labelled sites whereas intermediate levels were found in the posterior lobe. There was a partial overlap between sst2 receptor mRNA and [125I]Tyr3-octreotide binding, although the distribution of the binding sites was much wider than that of receptor mRNA. The same observation was made for sst1 and/or sst4 receptor mRNA and [125I]CGP 23996 labelled sites. The present data show that SRIF1 and SRIF2 receptors are present in the human brain with different distributions, especially in the cerebral cortex and the pituitary. The very similar distribution of sites labelled with [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide suggests (i) that sst2 receptors are predominant within the SRIF1 family in the human brain and (ii) that [125I]LTT-SRIF-28 under the conditions used in the present study, does not significnatly label SRIF2 sites.
authors.affiliation: Preclinical Research, SANDOZ, Pharma Ltd., Basel, Switzerland.
authors.forename: V S
authors.initials: VS
authors.lastname: Thoss
authors.forename: C
authors.initials: C
authors.lastname: Piwko
authors.forename: A
authors.initials: A
authors.lastname: Probst
authors.forename: D
authors.initials: D
authors.lastname: Hoyer
mesh_terms: D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D015282:Octreotide / Q000031:analogs & derivatives / Q000378:metabolism; D009928:Organ Specificity; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; C045210:3-Tyr-octreotide; D013004:Somatostatin; C038136:CGP 23996; C093733:somatostatin receptor 2; D015282:Octreotide