Somatostatin receptor subtype expression in cells of the rat immune system during adjuvant arthritis.

Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter and may also have an immunomodulatory role. The genes for five subtypes of somatostatin receptors (sst) have been cloned, suggesting that the diverse effects of the peptide might be mediated by different receptors. We are interested in studying the role of sst ininflammation, using an animal model. Because of the up-regulation of sst expression in inflamed joints in human rheumatoid arthritis, we chose rat adjuvant arthritis as an experimental model. In order to determine which of the sst subtypes might be important in immune modulation, subtype expression in leukocytes isolated from different lymphoid tissues of the rat was studied. Also, the expression levels of the most abundantly expressed sst mRNAs in leukocytes from spleen and blood were compared in rats with adjuvantarthritis and controls, using a semi-quantitative approach. Furthermore, the effect of systemic administration of a long-acting somatostatin analogue, octreotide, which binds selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the severity of rat adjuvant arthritis, was studied. The main sst expressed in cells of the rat immune system, both resting and activated, were found to be sst3 and sst4. This contrasts with the human and murine situations, in which sst2 appears to be the main subtype expressed in the immune system. No quantitative differences in sst subtype mRNA levels in leukocytes from spleen and blood were found between rats with adjuvant arthritis and controls. Finally, no effect of systemic administration of octreotide on either the incidence or severity of adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat adjuvant arthritis corroborates our finding that these sst subtypes are not expressed in cells of the rat immune system. In conclusion, cells of the rat immune system appear to express a spectrum of sst (sst3 and sst4) different from that found in human granulomatous and autoimmune disease (mainly sst2). Therefore, the rat adjuvant arthritis model appears to be suitable only for studying the immunomodulatory effects of somatostatin analogues which have a high affinity for sst3 and sst4, but not for studying the immunomodulatory effects of octreotide, which has a high affinity only for sst2 and sst5.

[1]  K. Bost,et al.  Substance P-induced IL-12 production by murine macrophages. , 1997, Journal of immunology.

[2]  S. Melmed,et al.  Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. , 1997, The Journal of clinical investigation.

[3]  J. Laissue,et al.  Somatostatin receptors and their subtypes in human tumors and in peritumoral vessels. , 1996, Metabolism: clinical and experimental.

[4]  H. Loh,et al.  Activation of rat thymocytes selectively upregulates the expression of somatostatin receptor subtype-1. , 1996, Biochemistry and molecular biology international.

[5]  Lars Klareskog,et al.  Oil-induced arthritis in DA rats: tissue distribution of arthritogenic 14C-labelled hexadecane. , 1995, International journal of immunopharmacology.

[6]  E. Krenning,et al.  Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis. , 1994, European journal of pharmacology.

[7]  D. Elliott,et al.  T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA. , 1994, Journal of immunology.

[8]  N. Vaysse,et al.  Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. , 1994, Molecular pharmacology.

[9]  S. Seino,et al.  Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. , 1994, The Journal of clinical investigation.

[10]  M. Berelowitz,et al.  Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat. , 1993, Endocrinology.

[11]  W. Meyerhof,et al.  Expression Patterns of Rat Somatostatin Receptor Genes in Pre‐ and Postnatal Brain and Pituitary , 1993, Journal of neurochemistry.

[12]  M. Berelowitz,et al.  Molecular cloning and functional expression of a brain-specific somatostatin receptor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Weis,et al.  Development of a sensitive reverse transcriptase PCR assay, RT-RPCR, utilizing rapid cycle times. , 1992, PCR methods and applications.

[14]  W. Meyerhof,et al.  Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Snyder,et al.  Cloning and expression of a rat somatostatin receptor enriched in brain. , 1992, The Journal of biological chemistry.

[16]  C. Saper,et al.  Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase. , 1992, The Journal of biological chemistry.

[17]  H. Lübbert,et al.  Expression cloning of a rat brain somatostatin receptor cDNA. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[18]  W. Meyerhof,et al.  Cloning of a cDNA encoding a novel putative G-protein-coupled receptor expressed in specific rat brain regions. , 1991, DNA and cell biology.

[19]  J. Charboneau,et al.  Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. , 1990, Cancer research.

[20]  P. Brazeau,et al.  Somatostatin: a peptide with unexpected physiologic activities. , 1986, The American journal of medicine.

[21]  J. Reubi.  New specific radioligand for one subpopulation of brain somatostatin receptors. , 1985, Life sciences.

[22]  S. Reichlin.  Somatostatin. , 1983, The New England journal of medicine.

[23]  Van Arman Cg.  Pathway to adjuvant arthritis. , 1976 .

[24]  B. Vernon‐roberts,et al.  Adjuvant arthritis in the rat , 1976, Annals of the rheumatic diseases.

[25]  S. Lamberts,et al.  17-β-Estradiol-Dependent Regulation of Somatostatin Receptor Subtype Expression in the 7315b Prolactin Secreting Rat Pituitary Tumor in Vitro and in Vivo. , 1997, Endocrinology.

[26]  B. Steiniger,et al.  High-yield purification of rat monocytes by combined density gradient and immunomagnetic separation. , 1996, Journal of immunological methods.

[27]  T. Visser,et al.  In vitro and in vivo studies of substance P receptor expression in rats with the new analog [indium-111-DTPA-Arg1]substance P. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  A. Iagnocco,et al.  Intra-articular somatostatin 14 reduces synovial thickness in rheumatoid arthritis: an ultrasonographic study. , 1995, International journal of clinical pharmacology research.

[29]  P. M. Vanhagen,et al.  The Presence of Somatostatin Receptors in Rheumatoid Arthritis , 1994 .

[30]  D. Hoyer,et al.  Differential expression of five somatostatin receptor subtypes, SSTR1-5, in the CNS and peripheral tissue. , 1994, Digestion.