Distribution and characterisation of somatostatin receptor mRNA and binding sites in the brain and periphery

• Published in: Journal of physiology, Paris Vol. 94; no. 3; pp. 265 - 281
• Main Authors: Fehlmann, Dominique, Langenegger, Daniel, Schuepbach, Edy, Siehler, Sandra, Feuerbach, Dominik, Hoyer, Daniel
• Format: Journal Article
• Language: English
• Published: France Elsevier Ltd 01.05.2000
• Subjects: Animals; Autoradiography; Brain Chemistry - genetics; Cloning, Molecular; distribution; Gene Expression - physiology; Guinea Pigs; guinea-pig brain; Ileum - chemistry; in situ hybridisation; In Situ Hybridization; Iodine Radioisotopes; Lung - chemistry; Male; Membrane Proteins; Mice; Mice, Inbred Strains; mouse; mRNA expression; Pancreas - chemistry; Radioligand Assay; radioligand binding; rat; Rats; Receptors, Somatostatin - genetics; Receptors, Somatostatin - metabolism; RNA, Messenger - analysis; somatostatin receptors; Species Specificity; guinea-pig brain; mouse; in situ hybridisation; rat; autoradiography; somatostatin receptors; radioligand binding; distribution; mRNA expression
• ISSN: 0928-4257; 1769-7115
• DOI: 10.1016/S0928-4257(00)00208-4

The distribution and nature of (somatostatin) SRIF receptors and receptor mRNAs was studied in the brain and periphery of various laboratory animals using in situ hybridisation, autoradiography and radioligand binding. The messenger RNA (mRNA) expression of SRIF receptors msst 1, msst 2, msst 3, msst 4 and msst 5 was studied in the adult mouse brain by in situ hybridisation histochemistry using specific oligonucleotide probes and compared to that of adult rats. As observed in rat brain, sst 3 receptor mRNA is prominently expressed across the mouse brain, although equivalent binding has not yet been identified in situ. Sst 1 and sst 2 receptor mRNA expression, was prominent and again comparable to that observed in rat brain, whereas sst 4 and especially sst 5 receptor mRNA show comparatively low levels, although the former appears to be widely distributed while the latter could only be identified in a few nuclei. Altogether, the data are compatible with current knowledge, i.e. sst 1 and sst 2 receptor mRNA is prominent (both receptors have been functionally identified in the brain and for sst 2 in the periphery), sst 3 mRNA is highly expressed but in the absence of any functional correlate remains elusive. The expression of sst 4 mRNA is comparatively low (especially when compared to what is seen in the lung, where high densities of sst 4 receptors are present) and it remains to be seen whether sst 5 receptor mRNA, which is confined to a few nuclei, will play a role in the brain, keeping in mind that high levels are found in the pituitary. Radioligand binding studies were performed in CCL39 cells expressing the five human recombinant receptors and compared to binding in membranes of rat cerebral cortex with [ 125I]Tyr 11-SRIF 14 which in the presence of 120 mM labels primarily sst 1 receptor as suggested by the better correlation hsst 1 and similar rank order of potency. The profile of [ 125I]Tyr 3-octreotide labelled sites in rat cortex correlates better with recombinant sst 2 than sst 3 or sst 5 binding profiles. Finally, [ 125I]LTT-SRIF 28-labelled sites in rat lung express a sst 4 receptor profile in agreement with previous findings. SRIF receptor autoradiography was performed in the brain and peripheral tissue of rat and/or guinea-pig using a number of ligands known to label recombinant SRIF receptors: [ 125I]LTT-SRIF 28, [ 125I]CGP 23996, [ 125I]Tyr 10-CST, or [ 125I]Tyr 3-octreotide. Although, [ 125I]Tyr 10-CST has been shown to label all five recombinant SRIF receptors, it is apparent that this radioligand is not useful for autoradiographic studies. By contrast, the other three ligands show good signal to noise ratios in rat or guinea-pig brain, rat lung, rat pancreas, or guinea-pig ileum. In most tissues, [ 125I]Tyr 3-octreotide represents a prominent part of the binding (when compared to [ 125I]LTT-SRIF 28 and [ 125I]CGP 23996), suggesting that sst 2 receptors are strongly expressed in most tissues; it is only in rat lung that [ 125I]LTT-SRIF 28 and [ 125I]CGP 23996 show marked binding, whereas [ 125I]Tyr 3-octreotide does apparently label no sites, in agreement with the sole presence of sst 4 receptors in this tissue.