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.

Broad characterization of endogenous peptides in the tree shrew visual system

“…Somatostatins are expressed by about one third of GABAergic interneurons, and about 90% of SOM neurons are GABAergic [45]. We observed a high abundance of SOM 28 in the primary visual cortex, consistent with previous findings obtained using radiography evaluation of binding sites in the human brain [46,47], as well as in cat and monkey [48]. In contrast, we found that SOM 28 AA1-12 was present at high abundance in the superior colliculus.…”

Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist

“…The implications of veldoreotide activity at the SST4 receptor are multifold, albeit not entirely clear, given, in part, the lack of antibodies specific to the human SST4 receptor [ 2 ]. However, the clinical utility of an SSA that binds to the SST4 receptor is promising in light of the widespread expression of the SST4 receptor from the brain to the immune system [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Upregulation of SST4 receptors in patients with chronic pulmonary inflammation suggests that the SST4 receptor agonists may have therapeutic potential in inflammatory lung conditions [ 11 ].…”

“…The role of the SST4 receptor in the human body is not entirely clear, but its expression has been shown in the brain, the duodenum, the kidney, the lung, the non-islet cells of the pancreas, the parathyroid gland, the placenta, the stomach, and the T cells [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The protective role of this receptor was demonstrated in experimental models of chronic arthritis, airway inflammation, and skin hypersensitivity in mice lacking the SST4 receptor, with knock-out mice presenting with more-severe contact dermatitis, increased lung edema and bronchial inflammation, and greater inflammatory hyperalgesia compared with their SST4 receptor-expressing littermates [ 16 ].…”

Expression of Somatostatin Receptors 1 and 2 in Human Choroid Plexus and Arachnoid Granulations

“…Strong SSTR1-ir and SSTR2-ir in CP are consistent with the previously published results by Thoss and colleagues. 14 The SST analogues used in that study bind more than 1 receptor subtype. Those results were suggestive of but not conclusive for the presence of any specific SSTRs on CP.…”