Regional distribution of somatostatin receptor affinity states in rat brain: effects of divalent cations and GTP

Moyse, Emmanuel; Slama, A.; Videau, Catherine; Ángela, Paulina; Kordon, C.; Epelbaum, Jacques

doi:10.1016/0167-0115(89)90190-0

Cited by 28 publications

(16 citation statements)

References 23 publications

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“…2) (44). Thus, the SRIF receptor is a member of the receptor family with seven membrane-spanning regions, which is also suggested by its coupling to a G protein (12)(13)(14). A number of amino acid residues that are conserved in this family of receptors are also found in this sequence (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Radiolabeled SRIF analogs have been used extensively to characterize the binding properties of SRIF receptors on the various target tissues. Previously, it has been shown that SRIF receptors are coupled to GTP-binding proteins (G proteins) (12)(13)(14)(15) In the present study we describe the isolation and primary structure of a SRIF receptor cDNA, the pharmacology of the expressed receptor, and the distribution of the mRNA. * The approach chosen for cloning of the receptor cDNA included the construction of a cDNA expression library with RNA isolated from the developing rat cortex and hippocampus, transfection of pools of clones into COS-1 cells, and identification of cells expressing SRIF receptors by autoradiography after binding of iodinated ligands (21,22).…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression cloning of a rat brain somatostatin receptor cDNA.

Kluxen

Berthou

Lübbert

1992

Proc. Natl. Acad. Sci. U.S.A.

167

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We have used an expression-cloning strategy to isolate a cDNA encoding a somatostatin (somatotropin release-inhibiting factor, SRIF) receptor from rat cortex and hippocampus. A positive clone was identified by autoradlography after binding of radiolabeled SRIF to COS-1 cells previously transfected with pools of cDNA clones. The deduced amino acid sequence of the receptor displays sequence and structural homology to the family of G-protein-coupled receptors. The affinity of various SRIF analogs to the expressed receptor resembles their effects on growth hormone release from pitnitary cells. In addition, the dbution of the mRNA in various tissues corresponds to that described for native SRIF receptors. Therefore, we conclude that we have isolated a rat brain SRIF receptor cDNA.Somatostatin (somatotropin release-inhibiting factor, SRIF), a neuropeptide initially isolated from the hypothalamus, was shown to act on many different cell types by inhibiting the secretion of hormones, including growth hormone (GH), insulin, glucagon, gastrin, and secretin (1-3). In addition, SRIF was shown to act as a neurotransmitter (4-6). Therefore, SRIF has widespread functions as a modulator of neuronal activity as well as endocrine and exocrine secretion. These regulatory effects are mediated by specific membrane receptors on the SRIF target tissues (7). High-affinity, saturable binding sites have been demonstrated in cortex, hippocampus, substantia nigra, pituitary gland, pancreas, adrenal cortex, and several tumor types-for instance, endocrine, breast, lung, or brain tumors (8)(9)(10)(11). Radiolabeled SRIF analogs have been used extensively to characterize the binding properties of SRIF receptors on the various target tissues. Previously, it has been shown that SRIF receptors are coupled to GTP-binding proteins (G proteins) (12)(13)(14)(15) In the present study we describe the isolation and primary structure of a SRIF receptor cDNA, the pharmacology of the expressed receptor, and the distribution of the mRNA.* The approach chosen for cloning of the receptor cDNA included the construction of a cDNA expression library with RNA isolated from the developing rat cortex and hippocampus, transfection of pools of clones into COS-1 cells, and identification of cells expressing SRIF receptors by autoradiography after binding of iodinated ligands (21,22). MATERIALS AND METHODScDNA Cloing. RNA was purified from cortex and hippocampus dissected from brains of 6-day-old rats by the guanidinium thiocyanate/acid phenol method (23). Poly(A)+ RNA was enriched by two subsequent passages over an oligo(dT)-cellulose column as described (24). Five micrograms of poly(A)+ RNA was used in the synthesis of oligo(dT)-primed double-stranded cDNA using the Amersham cDNA synthesis system. After addition ofphosphorylated Dra III adapters (pGTC GAC CAC CTC and pGTG GTC GAC) the cDNAs were size-selected by gel filtration [Sepharose CL-2B (Pharmacia), 39 x 1.5 cm column; running buffer = 1 M KCI/35 mM Tris'HCl, pH 8.3/30 mM KH2PO4/1 mM EDTA; flow rate,...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Expression cloning of a rat brain somatostatin receptor cDNA.

Kluxen

Berthou

Lübbert

1992

Proc. Natl. Acad. Sci. U.S.A.

167

View full text Add to dashboard Cite

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“…of three determinations and used to generate displacement curves and obtain K i values. Competition curves were analysed by non-linear regression using the Parker and Waud model (48) which allows for statistical evaluation of dissociation constant kinetics.…”

Section: Discussionmentioning

confidence: 99%

Species differences between male rat and ram pituitary somatostatin receptors involved in the inhibition of growth hormone secretion

Briard

Dutour

Epelbaum

et al. 1997

European Journal of Endocrinology

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The sheep is a valuable model in which to study GH neuroregulation as its pattern of GH secretion is very close to that in humans. Furthermore, important differences in somatostatin (SRIH) action between rats and sheep have been found previously. Our goal was to compare in male rat and ram pituitaries the binding characteristics of somatostatin receptors and the effect of SRIH and 17 analogues on GH release. Using radioautography, SRIH binding was seen to be evenly distributed over the anterior pituitary of both species. In the binding assay, binding sites were three times more concentrated in rats than in sheep. Important interspecies differences in the action of SRIH and its analogues were found: they inhibited GH at lower concentrations in rats than in sheep. Seven peptides displayed greater inhibitory ability in sheep than in rats while three were more potent in rats. Agonistic potencies to inhibit GH release in rats were correlated with somatostatin receptors subtype 2 (sst2) affinities. Our data confirm and extend the quantitative differences between rat and sheep in SRIH inhibitory action on GH secretion and confirm that ligand-binding properties of a given receptor subtype cannot be extrapolated across species. European Journal of Endocrinology 137 545-555

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“…For pituitary, duplicate sections were incubated with 125 I-SRIH (0.1 n M ) and increasing amounts of unlabeled SRIH-14 (10 –11 to 10 –6 M ), as previously described [34]. After incubation, pituitary sections were processed as already described for brain sections.…”

Section: Methodsmentioning

confidence: 99%

Homologous Upregulation of sst2 Somatostatin Receptor Expression in the Rat Arcuate Nucleus in vivo

et al. 2001

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In vitro studies using various cell systems have provided conflicting results regarding homologous regulation of somatostatin (SRIH) receptors, and information on whether SRIH regulates the expression of its own receptors in vivo is lacking. In the present study we examined, by in situ hybridization, the effects of pretreatment with the sst2-preferring SRIH analog, octreotide, in vivo, on mRNA levels of two SRIH receptor subtypes, sst1 and sst2, in rat brain and pituitary. ¹²⁵I-[DTrp⁸]-SRIH binding was also measured in these regions. Three hours after the iv injection of 50 µg octreotide to conscious adult male rats, there was a 46% increase (p < 0.01) in the labeling density of sst2 mRNA-expressing cells in the hypothalamic arcuate nucleus compared to normal saline-pretreated controls, but not in any of the other brain regions examined. Computer-assisted image analysis revealed that 3 h exposure to octreotide significantly (p < 0.01) augmented both the number and labeling density of sst2 mRNA-expressing cells in the arcuate nucleus, compared to those in saline-treated controls. By contrast, within the anterior pituitary gland, in vivo exposure to octreotide did not affect the expression of sst2 mRNA. No changes in sst1 mRNA-expressing cells were observed after octreotide treatment in any of the regions measured, indicating that the observed effects were homologous, i.e. specific of the receptor subtype stimulated. Octreotide pretreatment was also without effect on the density of ¹²⁵I-[DTrp⁸]-SRIH binding in either the arcuate nucleus or pituitary. These results demonstrate, for the first time, that SRIH preexposure in vivo upregulates the expression of a subtype of its own receptors, sst2, within the central nervous system. They further suggest that pretreatment with SRIH in vivo does not cause sst2 receptor desensitization in arcuate nucleus and pituitary. Such homologous regulatory mechanisms may play an important role in the neuroendocrine control of growth hormone (GH) secretion by the arcuate nucleus.

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Regional distribution of somatostatin receptor affinity states in rat brain: effects of divalent cations and GTP

Cited by 28 publications

References 23 publications

Expression cloning of a rat brain somatostatin receptor cDNA.

Expression cloning of a rat brain somatostatin receptor cDNA.

Species differences between male rat and ram pituitary somatostatin receptors involved in the inhibition of growth hormone secretion

Homologous Upregulation of sst2 Somatostatin Receptor Expression in the Rat Arcuate Nucleus in vivo

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