Dissociation of somatostatin effects. Peptides inhibiting the release of growth hormone but not glucagon or insulin in rats

Grant, Norman H.; Clark, Donald R.; Garsky, Victor M.; Jaunakais, Ivars; McGregor, W.H.; Sarantakis, D.

doi:10.1016/0024-3205(76)90158-2

Cited by 27 publications

(5 citation statements)

References 4 publications

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“…Due to the rapid degradation and clearance of the native SRIF peptide, efforts were focused on creating analogs with increased metabolic stability that would be useful for treating conditions of excess GH secretion, most notably acromegaly. As the structure of native SST was modified, differences were observed in the ratio of GH-suppressing activity versus other actions, in particular the suppression of insulin, which was considered a potential problem for therapeutic application ( Grant et al, 1976 ; Brown et al, 1977 ; Meyers et al, 1977 ; Coy et al, 1978 ). Through screening in rodents, analogs were identified with potent GH-suppressing activity with acceptably low insulin-suppressing activity ( Bauer et al, 1982 ; Heiman et al, 1987 ), including the two SRIF analogs still most widely used clinically for treatment of acromegaly and NETs, octreotide (Sandostatin) and lanreotide (Somatuline) ( Fig.…”

Section: Multireceptor Somatotropin-release Inhibitory Factor Anamentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

et al. 2018

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Somatostatin, also known as somatotropin-release inhibitory factor, is a cyclopeptide that exerts potent inhibitory actions on hormone secretion and neuronal excitability. Its physiologic functions are mediated by five G protein–coupled receptors (GPCRs) called somatostatin receptor (SST)1–5. These five receptors share common structural features and signaling mechanisms but differ in their cellular and subcellular localization and mode of regulation. SST2 and SST5 receptors have evolved as primary targets for pharmacological treatment of pituitary adenomas and neuroendocrine tumors. In addition, SST2 is a prototypical GPCR for the development of peptide-based radiopharmaceuticals for diagnostic and therapeutic interventions. This review article summarizes findings published in the last 25 years on the physiology, pharmacology, and clinical applications related to SSTs. We also discuss potential future developments and propose a new nomenclature.

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Section: Multireceptor Somatotropin-release Inhibitory Factor Anamentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

et al. 2018

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“…There is an urgent need for a reliable animal model for testing the potency of structural analogs of somatostatin to inhibit insulin and glucagon release. As in previous reports Grant et al 1976), arginine was chosen to stimulate the secretion of insulin and glucagon. The infusion of arginine increased the plasma insulin level in the rat rapidly in 10 min, while the glucagon level rose more slowly to a maximum only after 30 min.…”

Section: Effect Of Injection Of Graded Doses Of Somatostatin On Arginmentioning

confidence: 99%

An in Vivo Model for Testing Inhibition of Arginine-Induced Insulin and Glucagon Release by Somatostatin Analogs

Gordin¹,

Meyers²,

Arimura³

et al. 1977

Acta Endocrinologica

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An animal model for testing the in vivo potency of somatostatin analogs in inhibiting the release of insulin and glucagon is described. The secretion of these pancreatic hormones was stimulated in rat by infusion of arginine. The plasma insulin level increased almost to a maximum after an infusion of 10 min, while plasma glucagon rose more slowly, reaching its maximum only after a 30 min infusion. Concomitant infusion of graded doses of somatostatin (2.5, 10, 40 and 160 \g=m\g/100g BW) for 30 min inhibited both insulin and glucagon release in a dose-dependent manner, enabling us to test somatostatin analogs for insulin and glucagon-suppressive activity in a semi-quantitative manner. Using this animal model, 3 analogs of somatostatin, [D-Cys14]-, [Ala2, D-Cys14]-and [D-Trp8, D-Cys14]somatostatin were tested in a 4-point assay. They all showed dissociated activity in inhibiting the secretion of glucagon more than that of insulin.Somatostatin was originally isolated because of its ability to inhibit the release of growth hormone (GH) in vitro and in invo (Brazeuau et al. 1973). Soma¬ tostatin was soon found to inhibit hormones other than GH, including glucagon and insulin, and even to inhibit the secretions of several exocrine glands (Hall et al. 1973;Mortimer et al. 1974;Hall 8c Gomez-Pan 1976). Somatostatin in-0 NIH Fogarty International Research Fellow.

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“…Other SS analogues with selective actions on the pituitary have been reported (13)(14)(15), although none was more active than SS.…”

mentioning

confidence: 98%

[Phe4]somatostatin: a potent, selective inhibitor of growth hormone release.

Meyers¹,

Coy²,

Murphy³

et al. 1980

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

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[Phe4]Somatostatin was twice as active as somatostatin (SS) in suppressing rat growth hormone release in vitro but had only weak activity toward inhibition of insulin and glucagon release in vivo. The ability of this analogue to inhibit growth hormone release more actively than SS was confirmed in vivo by two separately designed bioassays. Further structure/activity studies of position 4 were carried out with [Glu4]SS, [Thr4]SS, and des-Lys4-SS, all of which had negligible inhibiting activity in the pituitary and pancreas. In this context the strikingly selective activity of [Phe4]SS suggests a fundamental difference in the SS receptors of pituitary and pancreas and the normal side-chain basicity of position 4 appears to be more important for action in pancreas than in pituitary. [Phe4]SS has properties that may be useful in the development of agents for the treatment of acromegaly or other disorders associated with increased growth hormone levels.

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Dissociation of somatostatin effects. Peptides inhibiting the release of growth hormone but not glucagon or insulin in rats

Cited by 27 publications

References 4 publications

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

An in Vivo Model for Testing Inhibition of Arginine-Induced Insulin and Glucagon Release by Somatostatin Analogs

[Phe4]somatostatin: a potent, selective inhibitor of growth hormone release.

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