scholarly journals Co-purification of a protein tyrosine phosphatase with activated somatostatin receptors from rat pancreatic acinar membranes

1994 ◽  
Vol 303 (2) ◽  
pp. 441-448 ◽  
Author(s):  
M Zeggari ◽  
J P Esteve ◽  
I Rauly ◽  
C Cambillau ◽  
H Mazarguil ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Plasma Membranes ◽  
Radioligand Binding ◽  
Tyrosine Phosphatase ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Membrane Receptors ◽  
Receptor Binding Site ◽  
Receptor Complexes ◽  
Somatostatin 14

We have previously shown that somatostatin promotes the stimulation of a membrane tyrosine phosphatase activity in pancreatic cells. To gain insight into the mechanism of somatostatin action, we purified somatostatin-receptor complexes from somatostatin 28-prelabelled rat pancreatic plasma membranes by immunoaffinity chromatography using immobilized antibodies raised against the N-terminal part of somatostatin 28, somatostatin 28 (1-14), which is not involved in receptor-binding-site recognition. After SDS gel electrophoresis a band with a molecular mass of 87 kDa was identified in the affinity-purified material as the somatostatin receptor. The 87 kDa protein was not observed when the membrane receptors were solubilized in a free unoccupied or somatostatin 14-occupied form, or when nonimmune serum replaced the anti-[somatostatin 28 (1-14)] anti-serum. Somatostatin 14 inhibited the appearance of the 87 kDa protein in the same range of concentrations that inhibit radioligand binding on pancreatic membranes. After somatostatin 28 treatment of membranes, purified somatostatin receptor preparations exhibited an elevated tyrosine phosphatase activity that dephosphorylated phosphorylated epidermal growth factor receptor and poly(Glu,Tyr). This activity was related to the presence of somatostatin receptors in purified material. It was increased by dithiothreitol and inhibited by orthovanadate. In purified material containing somatostatin receptors, anti-[Src homology 2 domains (SH2)]-containing tyrosine phosphatase SHPTP1 polyclonal antibodies identified a protein of 66 kDa which was not detected in the absence of somatostatin receptor. Furthermore, the anti-SHPTP1 antibodies immunoprecipitated specific somatostatin receptors from somatostatin-prelabelled pancreatic membranes and from untreated membranes. These results indicate that a 66 kDa tyrosine phosphatase related to SHPTP1 co-purifies with the pancreatic somatostatin receptors, and suggest that this protein is associated with somatostatin receptors at the membrane level.

scholarly journals Somatostatin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Corinne Bosquet ◽  
Justo P. Castaño ◽  
Zsolt Csaba ◽  
Micheal Culler ◽  
Pascal Dournaud ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
The Body ◽  
Physiological Effects ◽  
Endogenous Ligand ◽  
Endogenous Ligands ◽  
Inhibiting Factor ◽  
Wide Range ◽  
Somatostatin 14

Somatostatin (somatotropin release inhibiting factor) is an abundant neuropeptide, which acts on five subtypes of somatostatin receptor (SST1-SST5; nomenclature as agreed by the NC-IUPHAR Subcommittee on Somatostatin Receptors [89]). Activation of these receptors produces a wide range of physiological effects throughout the body including the inhibition of secretion of many hormones. Endogenous ligands for these receptors are somatostatin-14 (SRIF-14) and somatostatin-28 (SRIF-28). cortistatin-14 has also been suggested to be an endogenous ligand for somatostatin receptors [56].

Immunopurification of somatostatin receptor associated with a tyrosine phosphatase activity

1992 ◽  
Vol 40 (2) ◽  
pp. 143
Author(s):  
J.P. Esteve ◽  
M. Zeggari ◽  
I. Rauly ◽  
C. Cambillau ◽  
H. Mazarguil ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Tyrosine Phosphatase ◽  
Somatostatin Receptor

scholarly journals Fates of endocytosed somatostatin sst2 receptors and associated agonists

1998 ◽  
Vol 336 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Jennifer A. KOENIG ◽  
Rejbinder KAUR ◽  
Iain DODGEON ◽  
J. Michael EDWARDSON ◽  
Patrick P. A. HUMPHREY
Keyword(s):  
Cell Surface ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Recycling ◽  
Extracellular Medium ◽  
Main Pathway ◽  
Surface Receptor ◽  
Receptor Number ◽  
Agonist Ligands ◽  
Somatostatin 14

Somatostatin agonists are rapidly and efficiently internalized with the somatostatin sst2 receptor. The fate of internalized agonists and receptors is of critical importance because the rate of ligand recycling back to the cell surface can limit the amount of radioligand accumulated inside the cells, whereas receptor recycling might be of vital importance in providing the cell surface with dephosphorylated, resensitized receptors. Furthermore the accumulation of radioisotope-conjugated somatostatin agonists inside cancer cells resulting from receptor-mediated internalization has been used as a treatment for cancers that overexpress somatostatin receptors. In the present study, radio-iodinated agonists at the sst2 somatostatin receptor were employed to allow quantitative analysis of the fate of endocytosed agonist. After endocytosis, recycling back to the cell surface was the main pathway for both 125I-labelled somatostatin-14 (SRIF-14) and the more stable agonist 125I-labelled cyclo(N-Me-Ala-Tyr-d-Trp-Lys-Abu-Phe) (BIM-23027; Abu stands for aminobutyric acid), accounting for 75–85% of internalized ligand when re-endocytosis of radioligand was prevented. We have shown that there is a dynamic cycling of both somatostatin agonist ligands and receptors between the cell surface and internal compartments both during agonist treatment and after surface-bound agonist has been removed, unless steps are taken to prevent the re-activation of receptors by recycled agonist. Internalization leads to increased degradation of 125I-labelled SRIF-14 but not 125I-labelled BIM-23027. The concentration of recycled agonist accumulating in the extracellular medium was sufficient to re-activate the receptor, as measured both by the inhibition of forskolin-stimulated adenylate cyclase and the recovery of surface receptor number after internalization.

Structural characterization of PACAP receptors on rat liver plasma membranes

1993 ◽  
Vol 265 (5) ◽  
pp. G811-G818
Author(s):  
T. D. Nguyen ◽  
G. G. Heintz ◽  
M. S. Wolfe
Keyword(s):  
Rat Liver ◽  
Plasma Membranes ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Membrane Receptors ◽  
Receptor Complexes ◽  
High Affinity ◽  
Liver Plasma Membranes ◽  
Rat Liver Plasma Membranes ◽  
Pacap Receptors

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and PACAP-27 are recently characterized hypothalamic peptides with marked homology with vasoactive intestinal peptide (VIP), which are concentrated in the innervation of the digestive tract. We now report that, on rat liver plasma membranes, PACAP interacts with at least two types of receptors: receptors demonstrating equally high affinity for PACAP and VIP and receptors with high affinity for PACAP but low affinity for VIP. In contrast, on rat intestinal epithelial cell laterobasal membranes, only receptors with high affinities for PACAP and VIP were observed. After 125I-labeled VIP or 125I-labeled PACAP-27 was cross-linked to the liver plasma membrane receptors with the use of either disuccinimidosuberate or disuccinimido dithiobis(propionate), analysis of the resulting ligand-receptor complexes on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the structures of the VIP and PACAP receptors were similar: both ligand-receptor complexes displayed two radioactive bands with relative molecular weights of 80,000 and 56,000 under reducing conditions and of 75,000 and 53,000 under nonreducing conditions. These findings suggest that the receptors for the PACAP peptides and VIP are closely related, reflecting the marked homology between these peptides. The presence of receptors specific for PACAP on rat liver plasma membranes should stimulate further studies of the interaction between PACAP and the liver.

scholarly journals Immunohistochemical Expression of Somatostatin Receptor Subtypes in a Panel of Neuroendocrine Neoplasias

2019 ◽  
Vol 67 (10) ◽  
pp. 735-743 ◽  
Author(s):  
Satu M. Remes ◽  
Helena L. Leijon ◽  
Tiina J. Vesterinen ◽  
Johanna T. Arola ◽  
Caj H. Haglund
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Membrane Receptors ◽  
Receptor Subtypes ◽  
Receptor Imaging ◽  
Primary Tumors ◽  
Somatostatin Receptor Subtypes ◽  
Negative Controls ◽  
G Protein Coupled

Neuroendocrine neoplasias (NENs) are known to express somatostatin receptors (SSTRs) 1–5, which are G-protein-coupled cell membrane receptors. Somatostatin receptor imaging and therapy utilizes the SSTR expression. Synthetic somatostatin analogs with radioligands are used to detect primary tumors, metastases, and recurrent disease. Receptor analogs are also used for treating NENs. Furthermore, commercially available SSTR antibodies can be used for the immunohistochemical (IHC) detection of SSTRs. We investigated different SSTR antibody clones applying diverse IHC protocol settings to identify reliable clones and feasible protocols for NENs. A tissue microarray including NENs from 12 different primary sites were stained. Only UMB clones were able to localize SSTR on the cell membranes of NENs. SSTR2 (UMB1) emerged as the most common subtype followed by SSTR5 (UMB4) and SSTR1 (UMB7). SSTR3 (UMB5) expression was mainly cytoplasmic. Yet, SSTR4 expression was weak and located primarily in the cytoplasm. Thus, appropriate IHC protocols, including proper positive and negative controls, represent requirements for high-quality NEN diagnostics and for planning personalized therapy.

Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes

2016 ◽  
Vol 27 (1) ◽  
pp. 1-25 ◽  
Author(s):  
Luigi F. Agnati ◽  
Diego Guidolin ◽  
Chiara Cervetto ◽  
Dasiel O. Borroto-Escuela ◽  
Kjell Fuxe
Keyword(s):  
Plasma Membranes ◽  
Membrane Receptors ◽  
General Point ◽  
Target Cells ◽  
Special Focus ◽  
Receptor Subtypes ◽  
Receptor Complexes ◽  
Communication Processes ◽  
Receptor Interactions

AbstractIntercellular and intracellular communication processes consist of signals and recognition/decoding apparatuses of these signals. In humans, the G protein-coupled receptor (GPCR) family represents the largest family of cell surface receptors. More than 30 years ago, it has been proposed that GPCR could form dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane level and receptor-receptor interactions [RRIs] have been proposed as a new integrative mechanism for chemical signals impinging on cell plasma membranes). The basic phenomena involved in RRIs are allostery and cooperativity of membrane receptors, and the present paper provides basic information concerning their relevance for the integrative functions of RMs. In this context, the possible role of iso-receptor RM is discussed (with a special focus on dopamine receptor subtypes and on some of the RMs they form with other dopamine iso-receptors), and it is proposed that two types of cooperativity, namely, homotropic and heterotropic cooperativity, could allow distinguishing two types of functionally different RMs. From a general point of view, the presence of iso-receptors and their topological organization within RMs allow the use of a reduced number of signals for the intercellular communication processes, since the target cells can recognize and decode the same signal in different ways. This theoretical aspect is further analyzed here by means of an analogy with artificial information systems. Thus, it is suggested that the ‘multiplexer’ and ‘demultiplexer’ concepts could, at least in part, model the role of RMs formed by iso-receptors in the information handling by the cell.

scholarly journals Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours.

2003 ◽  
pp. 451-458 ◽  
Author(s):  
W W de Herder ◽  
L J Hofland ◽  
A J van der Lely ◽  
S W J Lamberts
Keyword(s):  
Neuroendocrine Tumours ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Carcinoid Tumours ◽  
High Affinity ◽  
Pancreatic Neuroendocrine Tumours ◽  
Predominant Expression ◽  
Somatostatin 14

Five somatostatin receptor (sst) subtype genes, sst(1), sst(2), sst(3), sst(4) and sst(5), have been cloned and characterised. The five sst subtypes all bind natural somatostatin-14 and somatostatin-28 with high affinity. Endocrine pancreatic and endocrine digestive tract tumours also express multiple sst subtypes, but sst(2) predominance is generally found. However, there is considerable variation in sst subtype expression between the different tumour types and among tumours of the same type. The predominant expression of sst(2) receptors on pancreatic endocrine or carcinoid tumours is essential for the control of hormonal hypersecretion by the octapeptide somatostatin analogues such as octreotide and lanreotide. Somatostatin and its octapeptide analogues are also able to inhibit proliferation of normal and tumour cells. The high density of sst(2) or sst(5) on pancreatic endocrine or carcinoid tumours further allows the use of radiolabelled somatostatin analogues for in vivo visualisation. The predominant expression of sst(2) receptors in these tumours and the efficiency of sst(2) receptors to undergo agonist-induced internalisation is also essential for the application of radiolabelled octapeptide somatostatin analogues. Currently, [(111)In-DTPA(0)]octreotide, [(90)Y-DOTA(0),Tyr(3)]octreotide, [(177)Lu-DOTA(0)Tyr(3)]octreotate, [(111)In-DOTA(0)]lanreotide and [(90)Y-DOTA(0)]lanreotide can be used for this purpose.

Somatostatin-28 regulates GLP-1 secretion via somatostatin receptor subtype 5 in rat intestinal cultures

2002 ◽  
Vol 283 (2) ◽  
pp. E311-E317 ◽  
Author(s):  
Connie Chisholm ◽  
Gordon R. Greenberg
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
High Specificity ◽  
Intestinal Cell ◽  
Receptor Subtype ◽  
Fetal Rat ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Somatostatin 14

Five somatostatin receptors (SSTRs) bind somatostatin-14 (S-14) and somatostatin-28 (S-28), but SSTR5 has the highest affinity for S-28. To determine whether S-28 acting through SSTR5 mediates inhibition of glucagon-like peptide-1 (GLP-1), fetal rat intestinal cell cultures were treated with somatostatin analogs with relatively high specificity for SSTRs 2–5. S-28 dose-dependently inhibited GLP-1 secretion stimulated by gastrin-releasing peptide more potently than S-14 (EC50 0.01 vs. 5.8 nM). GLP-1 secretion was inhibited by an SSTR5 analog, BIM-23268, more potently than S-14 and nearly as effectively as S-28. The SSTR5 analog L-372,588 also suppressed GLP-1 secretion equivalent to S-28, but a structurally similar peptide, L-362,855 (Tyr to Phe at position 7), was ineffective. An SSTR2-selective analog was less effective than S-28, and an SSTR3 analog was inactive. Separate treatment with GLP-1-(7–36)-NH2 increased S-28 and S-14 secretion by three- and fivefold; BIM-23268 abolished S-28 without altering S-14, whereas the SSTR2 analog was inactive. The results indicate that somatostatin regulation of GLP-1 secretion occurs via S-28 through activation of SSTR5. GLP-1-stimulated S-28 secretion is also autoregulated by SSTR5 activation, suggesting a feedback loop between GLP-1 and S-28 modulated by SSTR5.

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