Characterization and distribution of somatostatin SS-1 and SRIF-1 binding sites in rat brain: identitity with SSTR-2 receptors

Schoeffter, Philippe; Pérez, Julio; Langenegger, Daniel; Schüpbach, E.; Bobirnac, Ionel; Lübbert, Hermann; Berthou, Christian; Hoyer, Daniel

doi:10.1016/0922-4106(95)90180-9

Cited by 48 publications

(35 citation statements)

References 37 publications

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“…Recently, the development of antisera against selective peptide sequences of the sst2A receptor has allowed us (Dournaud et al, 1996) and others (Schindler et al, 1997) to document the distribution of this receptor protein in rat brain by immunocytochemistry. This distribution conformed for the most part to that of SRIF binding sites detected using either nonselective (for review, see Krantic et al, 1992) or sst2-preferring (Reubi and Maurer, 1985;Krantic et al, 1989Krantic et al, , 1990Martin et al, 1991;Schoeffter et al, 1995;Holloway et al, 1996) ligands, suggesting that other SRIF receptor subtypes are expressed within the same regions (Dournaud et al, 1996;Schindler et al, 1997). However, there were marked regional differences in the light microscopic distribution of sst2A protein: in some areas, immunolabeled receptors were selectively associated with neuronal perikarya and dendrites, whereas in others they appeared diff usely distributed throughout the tissue (Dournaud et al, 1996).…”

supporting

confidence: 70%

“…This immunolabeling was no longer observed when sections were incubated with immune serum preadsorbed with an excess of antigenic peptide. The distribution of SRIF immunoreactivity, as observed in sections adjacent to the ones processed for the sst2A receptor, was b Based on literature data on the distribution and densities of radioautographic labeling obtained using sst2-preferring ligands (Reubi and Maurer, 1985;Krantic et al, 1989Krantic et al, , 1990Martin et al, 1991;Schoeffter et al, 1995;Holloway et al, 1996). also similar to that published earlier (Johannson et al, 1984).…”

Section: Comparative Distribution Of Sst2a Receptors and Srif Axons Amentioning

confidence: 99%

“…Autoradiographic receptor binding studies have shown a widespread but selective distribution of SRI F binding sites in mammalian brain (Martin et al, 1991;Krantic et al, 1992;Moyse et al, 1992;Schoeffter et al, 1995;Holloway et al, 1996). Recently, the development of antisera against selective peptide sequences of the sst2A receptor has allowed us (Dournaud et al, 1996) and others (Schindler et al, 1997) to document the distribution of this receptor protein in rat brain by immunocytochemistry.…”

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confidence: 99%

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Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

Dournaud

Boudin²,

Schönbrunn³

et al. 1998

J. Neurosci.

115

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Using an antipeptide antibody, we reported previously on the distribution of the somatostatin sst2A receptor subtype in rat brain. Depending on the region, immunolabeled receptors were either confined to neuronal perikarya and dendrites or distributed diffusely in tissue. To investigate the functional significance of these distribution patterns, we examined the regional and cellular relationships between somatostatin axons and sst2A receptors in the rat CNS, using double-labeling immunocytochemistry. Light and confocal microscopy revealed a significant correlation ( p Ͻ 0.02) between the distribution of somatodendritic sst2A receptor immunoreactivity and that of somatostatin terminal fields, both quantitatively and qualitatively. Furthermore, in regions of somatodendritic labeling, a subpopulation of sst2A-immunoreactive cells was also immunopositive for somatostatin, suggesting that a subset of sst2A receptors consists of autoreceptors. By contrast, in regions displaying diffuse sst2A labeling only moderate to low densities of somatostatin terminals were observed, and no significant relationship was found between terminal density and receptor immunoreactivity.At the electron microscopic level, areas expressing somatodendritic sst2A labeling were found by immunogold cytochemistry to display low proportions of membrane-associated, as compared with intracellular, receptors. Conversely, in regions displaying diffuse sst2A receptor labeling, receptors were predominantly associated with neuronal plasma membranes, a finding consistent with the high density of sst2 binding sites previously visualized in these areas by autoradiography. Double-labeling studies demonstrated that in the former but not in the latter regions, sst2A-immunoreactive somata and dendrites were heavily contacted by somatostatin axon terminals. Taken together, these results suggest that the low incidence of membrane-associated receptors observed in regions of somatodendritic sst2A labeling may be caused by downregulation of cell surface receptors by endogenous somatostatin, possibly through ligand-induced receptor internalization.

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confidence: 70%

Section: Comparative Distribution Of Sst2a Receptors and Srif Axons Amentioning

confidence: 99%

mentioning

confidence: 99%

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Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

Dournaud

Boudin²,

Schönbrunn³

et al. 1998

J. Neurosci.

115

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“…Octreotide is the most commonly used SST 2 agonist (Vezzani et al, 1991;Hoyer et al, 1995;Perez et al, 1995;Schoeffter et al, 1995;Hicks et al, 1998). Application of 1 M octreotide resulted in 33.9% inhibition of epileptiform bursting in CA1 of wild-type mice (Table.…”

Section: Pharmacological Validation Of Receptor Knock-out Studiesmentioning

confidence: 99%

Somatostatin Receptor Subtype 4 Couples to the M-Current to Regulate Seizures

Qiu

Zeyda²,

Johnson³

et al. 2008

J. Neurosci.

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The K ϩ M-current (I M , Kv7) is an important regulator of cortical excitability, and mutations in these channels cause a seizure disorder in humans. The neuropeptide somatostatin (SST), which has antiepileptic properties, augments I M in hippocampal CA1 pyramidal neurons. We used SST receptor knock-out mice and subtype-selective ligands to investigate the receptor subtype that couples to I M and mediates the antiepileptic effects of SST. Using pentylenetetrazole as a chemoconvulsant, SST 2 , SST 3 , and SST 4 receptor knock-out mice all had shorter latencies to different seizure stages and increased seizure severity when compared with wild-type mice. However, the most robust differences were observed in the SST 4 knock-outs. When seizures were induced by systemic injection of kainate, only SST 4 knock-outs showed an increase in seizure sensitivity. We next examined the action of SST and subtype-selective SST agonists on electrophysiological parameters in hippocampal slices of wild-type and receptor knock-out mice. SST 2 and SST 4 appear to mediate the majority of SST inhibition of epileptiform activity in CA1. SST lacked presynaptic effects in mouse CA1, in contrast to our previous findings in rat. SST increased I M in CA1 pyramidal neurons of wild-type and SST 2 knock-out mice, but not SST 4 knock-out mice. Using M-channel blockers, we found that SST 4 coupling to M-channels is critical to its inhibition of epileptiform activity. This is the first demonstration of an endogenous enhancer of I M that is important in controlling seizure activity. SST 4 receptors could therefore be an important novel target for developing new antiepileptic and antiepileptogenic drugs.

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“…CHO-K1 cells, stably expressing the recombinant SREluciferase reporter gene, and human SRIF sst 2 receptors at levels which can be considered to be close to physiological (120 fmol mg À1 protein compared to 105 fmol mg À1 protein in rat cortex; Schoeffter et al, 1995), were cultured in Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 nutrient mix (1 : 1 þ glutamax I and pyridoxine), supplemented with 10% (v v À1 ) foetal bovine serum at 371C, 5% CO 2 , 95% relative humidity. Low concentrations of selection antibiotics were also included in the culture medium (geneticin sulphate (G418), 100 mg ml À1 and hygromycin B, 100 mg ml…”

Section: Cell Culturementioning

confidence: 99%

Comparison of functional profiles at human recombinant somatostatin sst₂ receptor: simultaneous determination of intracellular Ca²⁺ and luciferase expression in CHO‐K1 cells

Nunn

Cervia

Langenegger

et al. 2004

British J Pharmacology

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1 Somatostatin (somatotropin release inhibiting factor; SRIF) acts via five G protein-coupled receptors (sst 1 -sst 5 ) that modulate multiple cellular effectors. The aim of this study was to compare two functional effects of the human sst 2 receptor stably expressed in CHO-K1 cells in a single experiment using a duplex assay for intracellular calcium and serum response element (SRE)-driven luciferase expression. 2 Intracellular calcium was measured using a fluorometric imaging plate reader II (FLIPR II). SRIF-14 rapidly and transiently increased intracellular calcium with a pEC 50 of 8.7470.03 (n ¼ 52). At 5 h after FLIPR II measurements, luciferase expression was determined. SRIF-14 concentrationdependently increased luciferase expression (pEC 50 ¼ 9.0670.03, n ¼ 52). 3 Natural and synthetic agonist/antagonist ligands for SRIF receptors were tested in the duplex assay. Correlation of agonist potencies and efficacies between the two responses were significant (r 2 ¼ 0.83 and 0.90, pEC 50 and E max , respectively). 4 Pertussis toxin pretreatment reduced SRIF-14/octreotide-mediated intracellular calcium increases by 45-47% and luciferase expression by 95-98%. 5 Thapsigargin pretreatment abolished the SRIF-14/octreotide-mediated intracellular calcium increase but had no effect on luciferase expression. 6 In conclusion, SRIF stimulates an increase in intracellular calcium and SRE-luciferase expression via human sst 2 receptors in CHO-K1 cells.

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Characterization and distribution of somatostatin SS-1 and SRIF-1 binding sites in rat brain: identitity with SSTR-2 receptors

Cited by 48 publications

References 37 publications

Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

Somatostatin Receptor Subtype 4 Couples to the M-Current to Regulate Seizures

Comparison of functional profiles at human recombinant somatostatin sst₂ receptor: simultaneous determination of intracellular Ca²⁺ and luciferase expression in CHO‐K1 cells

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Characterization and distribution of somatostatin SS-1 and SRIF-1 binding sites in rat brain: identitity with SSTR-2 receptors

Cited by 48 publications

References 37 publications

Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

Interrelationships between Somatostatin sst2A Receptors and Somatostatin-Containing Axons in Rat Brain: Evidence for Regulation of Cell Surface Receptors by Endogenous Somatostatin

Somatostatin Receptor Subtype 4 Couples to the M-Current to Regulate Seizures

Comparison of functional profiles at human recombinant somatostatin sst2 receptor: simultaneous determination of intracellular Ca2+ and luciferase expression in CHO‐K1 cells

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Comparison of functional profiles at human recombinant somatostatin sst₂ receptor: simultaneous determination of intracellular Ca²⁺ and luciferase expression in CHO‐K1 cells