Last update 01 Nov 2024

UTS2R x SSTR

Last update 01 Nov 2024

Basic Info

Related Targets

UTS2RSSTR

Drugs associated with UTS2R x SSTR

SB-710411

Target

SSTR x UTS2R

Mechanism

SSTR antagonists [+1]

Active Org.-

Originator Org.

GlaxoSmithKline, Inc.

Active Indication-

Inactive Indication

Cardiovascular Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with UTS2R x SSTR

100 Translational Medicine associated with UTS2R x SSTR

0 Patents (Medical) associated with UTS2R x SSTR

Literatures (Medical) associated with UTS2R x SSTR

01 Dec 2019·EndocrinologyQ2 · MEDICINE

UTS2B Defines a Novel Enteroendocrine Cell Population and Regulates GLP-1 Secretion Through SSTR5 in Male Mice

Q2 · MEDICINE

Article

Author: Gubser Keller, Caroline ; Tang, Cong ; Stuber, Nathalie ; Weber, Delphine ; Reist, Matthias ; Nicholson, Thomas B ; Beibel, Martin ; Gaudet, Laurent ; Beck, Valerie ; Carbone, Walter ; Gapp, Berangere ; Siccardi, Noemie ; Ksiazek, Iwona ; Wirsching, Johann ; Bassilana, Frederic ; Mao, Xiaohong ; Surber, Sabrina Silvia ; Roma, Guglielmo

AbstractThe gut-pancreas axis plays a key role in the regulation of glucose homeostasis and may be therapeutically exploited to treat not only type 2 diabetes but also hypoglycemia and hyperinsulinemia. We identify a novel enteroendocrine cell type expressing the peptide hormone urotensin 2B (UTS2B). UTS2B inhibits glucagon-like peptide-1 (GLP-1) secretion in mouse intestinal crypts and organoids, not by signaling through its cognate receptor UTS2R but through the activation of the somatostatin receptor (SSTR) 5. Circulating UTS2B concentrations in mice are physiologically regulated during starvation, further linking this peptide hormone to metabolism. Furthermore, administration of UTS2B to starved mice demonstrates that it is capable of regulating blood glucose and plasma concentrations of GLP-1 and insulin in vivo. Altogether, our results identify a novel cellular source of UTS2B in the gut, which acts in a paracrine manner to regulate GLP-1 secretion through SSTR5. These findings uncover a fine-tuning mechanism mediated by a ligand-receptor pair in the regulation of gut hormone secretion, which can potentially be exploited to correct metabolic unbalance caused by overactivation of the gut-pancreas axis.

01 Jun 2014·Journal of Molecular EndocrinologyQ3 · MEDICINE

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Q3 · MEDICINE

Review

Author: Larhammar, Dan ; Quan, Feng B ; Lihrmann, Isabelle ; Ocampo Daza, Daniel ; Bougerol, Marion ; Bergqvist, Christina A ; Tostivint, Hervé

Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand–receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed threeSS(SS1,SS2, andSS5) and sixSSTR(SSTR1–6) genes, on the one hand, and fourUII(UII,URP,URP1, andURP2) and fiveUTS2R(UTS2R1–5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception ofSSTR4. Moreover, several additional genes have been gained through the 3R event, such asSS4and a second copy of theUII,SSTR2,SSTR3, andSSTR5genes, and through local duplications, such asSS3. In mammals, all the genes of the SSTR family have been preserved, with the exception ofSSTR6. In contrast, for the other families, extensive gene losses occurred, as only theSS1,SS2,UII, andURPgenes and oneUTS2Rgene are still present.

01 Mar 2004·Journal of Medicinal ChemistryQ1 · MEDICINE

Unraveling the Active Conformation of Urotensin II

Q1 · MEDICINE

Article

Author: Novellino, Ettore ; Rovero, Paolo ; Campiglia, Pietro ; Grieco, Paolo ; Carotenuto, Alfonso

Urotensin II (U-II) is a disulfide-bridged undecapeptide recently identified as the ligand of an orphan G-protein-coupled receptor. Human U-II (H-Glu-Thr-Pro-Asp-cyclo[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent vasoconstrictor compound identified to date. With the aim of elucidating the active conformation of hU-II, we have performed a spectroscopic analysis of hU-II minimal active fragment hU-II(4-11) in different environmental conditions. The analysis indicated that hU-II(4-11) was highly structured in the anisotropic membrane mimetic SDS solution, showing a type II' beta-turn structure, which is almost unprecedented for L-amino acid peptides. Micelle bound structure of hU-II(4-11) was then compared with those of four synthetic analogues recently synthesized in our lab, bearing modified Cys residues at position 5 and/or position 10 and characterized by different levels of agonist activity. The structures of the active compounds were found to be very similar to that of hU-II(4-11), while a barely active compound does not show any propensity to beta-turn formation. Furthermore, distances among putative pharmacophoric points in the structures of the active compounds obtained in SDS solution are in good agreement with those found in a recently described non-peptide agonist of the hU-II receptor. A type II' beta-turn structure was already found for the somatostatin analogue octreotide. On the basis of the similarity of the primary and 3D structures of U-II and somatostatin analogues and on the basis of the sequence homology between the GPR14/UT-II receptor and members of the somatostatin receptor family, a common evolutionary pathway for the signal transmission system activated by these peptide can be hypothesized.

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