Ring Size in Octreotide Amide Modulates Differently Agonist versus Antagonist Binding Affinity and Selectivity

Grace, Christy R.; Érchegyi, Judit; Samant, Manoj; Cescato, Renzo; Piccand, Véronique; Riek, Roland; Reubi, Jean Claude; Rivier, Jean

doi:10.1021/jm701445q

Cited by 21 publications

(21 citation statements)

References 30 publications

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“…Third, the selective sst 1 (S-406-062) or sst 4 (S-315-297) agonist (17,19) injected under the same conditions showed a trend toward decrease in water intake. In line with these findings, previous reports showed that the stable sst agonist octreotide, which is devoid of sst 1 and sst 4 affinity, while binding to sst 2 Ͼ sst 5 ϾϾ sst 3 (28), increased water consumption within the first 10 min after intracerebroventricular injection in picomolar range in rats that had no access to food (30).…”

Section: Discussionsupporting

confidence: 82%

Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior

Karasawa

Yakabi

Wang

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Intracerebroventricular injection of stable somatostatin (SST) agonists stimulates food and water intake in rats. We investigated the receptor subtype(s) involved in the dipsogenic effect of intracerebroventricular injection of SST agonists, mechanisms of action, and role. In nonfasted and non-water-deprived male rats with chronic intracerebroventricular cannula, intake of water without food or food without water was monitored separately to avoid any interactions compared with intracerebroventricular vehicle. SST-14 and cortistatin (CST-14) (1 μg/rat icv) increased water intake by 3.1- and 2.7-fold, respectively, while both peptides did not alter food intake at 1 h postinjection in the light phase. By contrast, the stable pan-somatostatin agonist ODT8-SST (1 μg/rat icv) increased both water and food intake by 4.9- and 3.7-fold, respectively. S-346-011, a selective receptor 2 (sst2) agonist (1 μg/rat icv) induced water ingestion, while sst1 or sst4 agonist, injected under the same conditions, did not. The sst2 antagonist S-406-028 (1 μg/rat icv) prevented the 1-h water intake induced by intracerebroventricular ODT8-SST and CST-14. Losartan (100 μg/rat icv), an angiotensin receptor 1 (AT1) antagonist, completely blocked the water consumption induced by intracerebroventricular ODT8-SST, whereas intracerebroventricular injection of S-406-028 did not modify the intracerebroventricular ANG II-induced dipsogenic response. The sst2 antagonist reduced by 40% the increase of the 3-h water intake in the early dark phase. These data indicate that SST-14 and CST-14 interact with sst2 to exert a potent dipsogenic effect, which is mediated downstream by angiotensin-AT1 signaling. These data also indicate that sst2 activation by brain SST-14 and/or CST-14 may play an important role in the regulation of drinking behavior.

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Section: Discussionsupporting

confidence: 82%

Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior

Karasawa

Yakabi

Wang

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Octreotide is a clinically used SST like peptide drug. Compared with native SST-14, octreotide has used more stable D-Trp for L-Trp and the ring size has been decreased from 12 to 6 [76]. When maintaining the receptor binding affinity of somatostatin, octreotide has a prolonged plasma half-life of about 100 min in humans.…”

Section: Chemical Modification Of a Peptidementioning

confidence: 99%

Peptide-based imaging agents for cancer detection

Sun

Liu

et al. 2017

Advanced Drug Delivery Reviews

191

151

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Selective receptor-targeting peptide based agents have attracted considerable attention in molecular imaging of tumor cells that overexpress corresponding peptide receptors due to their unique properties such as rapid clearance from circulation as well as high affinities and specificities for their targets. The rapid growth of chemistry modification techniques has enabled the design and development of various peptide-based imaging agents with enhanced metabolic stability, favorable pharmacokinetics, improved binding affinity and selectivity, better imaging ability as well as biosafety. Among them, many radiolabeled peptides have already been translated into the clinic with impressive diagnostic accuracy and sensitivity. This review summarizes the current status in the development of peptide-based imaging agents with an emphasis on the consideration of probe design including the identification of suitable peptides, the chemical modification of probes and the criteria for clinical translation. Specific examples in clinical trials have been provided as well with respect to their diagnostic capability compared with other FDA approved imaging agents.

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“… Affinities are derived from competitive radioligand displacement assays in cells stably expressing the cloned human receptor using 125 I-[Leu 8 DTrp 22 Tyr 25 ]SRIF-28 (Cescato et al, 2008; Erchegyi et al, 2003; Erchegyi et al, 2008; Erchegyi et al, 2009; Grace et al, 2006; Grace et al, 2008) except for somatostatin-14 (Viollet et al, 1995) and somatostatin-28 (Viollet et al, 1995). …”

Section: Figurementioning

confidence: 99%

The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior

Stengel

Karasawa

Taché

2015

Hormones and Behavior

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Somatostatin was discovered four decades ago as hypothalamic factor inhibiting growth hormone release. Subsequently, somatostatin was found to be widely distributed throughout the brain and to exert pleiotropic actions via interaction with five somatostatin receptors (sst1-5) that are also widely expressed throughout the brain. Interestingly, in contrast to the predominantly inhibitory actions of peripheral somatostatin, the activation of brain sst2 signaling by intracerebroventricular injection of stable somatostatin agonists potently stimulates food intake and independently, drinking behavior in rodents. The orexigenic response involves downstream orexin-1, neuropeptide Y1 and μ receptor signaling while the dipsogenic effect is mediated through the activation of the brain angiotensin 1 receptor. Brain sst2 activation is part of mechanisms underlying the stimulation of feeding and more prominently water intake in the dark phase and is able to counteract the anorexic response to visceral stressors.

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Ring Size in Octreotide Amide Modulates Differently Agonist versus Antagonist Binding Affinity and Selectivity

Abstract: H-DPhe 2 -c[Cys 3 -Phe 7 -DTrp 8 -Lys 9 -Thr 10

Cited by 21 publications

References 30 publications

Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior

Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior

Peptide-based imaging agents for cancer detection

The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior

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