Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural functional characteristics. receptors colocalized in neuronal subgroups, somatostatin is involved modulating dopamine-mediated control motor activity. However, the molecular basis for such interaction between unclear. Here, we show receptor D2R SSTR5 interact physically through hetero-oligomerization to create novel with enhanced Our results provide evidence from different G protein...

The existence of receptor dimers has been proposed for several G protein-coupled receptors. However, the question whether are necessary activating or modulating normal function is unclear. We address this with somatostatin receptors (SSTRs) which there five distinct subtypes. By using transfected mutant and wild type receptors, as well endogenous we provide pharmacological, biochemical, physical evidence, based on fluorescence resonance energy transfer analysis, that activation by ligand...

Heptahelical receptors (HHRs) are generally thought to function as monomeric entities. Several HHRs such somatostatin (SSTRs), however, form homo- and heterooligomers when activated by ligand binding. By using dual fluorescent ligands simultaneously applied live cells monotransfected with SSTR5 (R5) or SSTR1 (R1), cotransfected R5 R1, we have analyzed the receptor stoichiometry aggregation states for three systems fluorescence resonance energy transfer correlation spectroscopy. Both...

Expression of mRNA for the 5 somatostatin receptors (sst1–5) was characterized by Northern blot and RT-PCR analysis in 20 meningioma 9 glioma samples. sst1 detectable blots poly-A+ RNA meningiomas but not gliomas. In contrast, sst2 readily detected total as a major 2.3 kb transcript 2 minor 4.3 8 transcripts all 6 out Quantitation showed that 15 tumors expressed 1.3- to 33-fold higher levels than control normal human brain. Mean samples 978% Three gliomas 7- 14-fold brain whereas remaining...

Agonist regulation of somatostatin receptors (SSTRs) was investigated in stable CHO-K1 cells individually expressing the 5 human (h) SSTR subtypes. hSSTR 2,3,4, and displayed rapid agonist-dependent internalization [125I] LTT SST-28 ligand a time- temperature-dependent manner over 60 min. Maximum radioligand occurred with hSSTR3 (78%) followed by hSSTR5 (66%), hSSTR4 (29%) hSSTR2 (20%). In contrast, hSSTR1 virtually no internalization. Prolonged agonist treatment led to differential...

BACKGROUND We have analysed the distribution of five somatostatin receptors (sst1–5) by immunohistochemistry in a large retrospective series 51 medullary carcinoma thyroid (MCT) specimens and correlated pattern sst expression with (SRIF) peptide, tumour pathology clinical outcome. MEASUREMENTS Immunohistochemistry was performed rabbit polyclonal antipeptide antibodies directed against extracellular domains or cytoplasmic tail human (h) sst1–5. SRIF immunoreactivity investigated parallel...

Calcium-sensing receptor (CASR), expressed in parathyroid gland and kidney, is a critical regulator of extracellular calcium homeostasis. This G protein-coupled exists at the plasma membrane as homodimer, although it unclear which point biosynthetic pathway dimerization occurs. To address this issue, we have analyzed wild-type mutant CASRs harboring R66H, R66C or N583X-inactivating mutations identified familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroid patients, were...

Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells the central nervous system (CNS). Post-release from secretory or cells, first most appreciated role that SST exhibits antiproliferative effect target tissue served as potential therapeutic intervention various tumours of different origins. The SST-mediated vivo and/or vitro tumour considered direct via activation five somatostatin receptor subtypes (SSTR1-5), which are...

G-protein-coupled receptors (GPCRs) represent the largest and most diverse family of cell surface receptors. Several GPCRs have been documented to dimerize with resulting changes in pharmacology signaling. We previously reported, by means photobleaching fluorescence resonance energy transfer (pbFRET) microscopy correlation spectroscopic analysis live cells, that human somatostatin receptor (hSSTR) 5 could both homodimerize heterodimerize hSSTR1 presence agonist SST-14. By contrast, remained...

We have investigated the role of cytoplasmic tail (C-tail) human somatostatin receptor type 5 (hSSTR5) in regulating coupling to adenylyl cyclase (AC) and mediating agonist-dependent desensitization internalization responses. Mutant receptors with progressive C-tail truncation (Δ347, Δ338, Δ328, Δ318), Cys320→ Ala substitution (to block palmitoylation), or Tyr304→ a putative NPXXY motif were stably expressed Chinese hamster ovary K1 cells. Except for Tyr304 → mutant, which showed no binding,...

G-protein-coupled receptors (GPCRs) represent the largest and most diverse family of cell surface receptors. Several GPCRs have been documented to dimerize with resulting changes in pharmacology. We previously reported by means photobleaching fluorescence resonance energy transfer (pbFRET) microscopy correlation spectroscopic (FCS) analysis live cells, that human somatostatin receptor (hSSTR) 5 could both homodimerize heterodimerize hSSTR1 presence agonist SST-14. In contrast, remained...

OBJECTIVE—Heart disease is a leading cause of death in diabetes and could occur because excessive use fatty acid for energy generation. Our objective was to determine the mechanisms by which AMP-activated protein kinase (AMPK) augments cardiac lipoprotein lipase (LPL), enzyme that provides heart with majority its acid. RESEARCH DESIGN AND METHODS—We used diazoxide rats induce hyperglycemia or 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) thrombin directly stimulate AMPK p38...

Long term depression (LTD) in the CA1 region of hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced sleep-deprived (SD) rats. In present study, we investigated role metabotropic glutamate receptors (mGluRs), γ-Aminobutyric acid (GABA) B (GABAB-Rs) and N-methyl-D-aspartic (NMDARs) LTD population excitatory postsynaptic potential (pEPSP). The requirement Ca2+ from L- T- type voltage-gated calcium channels (VGCCs) intracellular stores was also studied. Results...

Somatostatin receptors (SSTRs) and opioid (ORs) belong to the superfamily of G-protein coupled function as negative regulators cell proliferation in breast cancer. In present study, we determined changes SSTR subtype 2 (SSTR2) μ, δ κ-ORs expression, signaling cascades apoptosis three different cancer cells namely MCF-7, MDA-MB231 T47D.Immunocytochemistry western blot analysis were employed study colocalization MAPKs (ERK1/2 p38), survival pathway (PI3K/AKT) tumor suppressor proteins (PTEN...

The peptide somatostatin (SST) is widely synthesized in the brain and periphery acts through a family of five receptors (SSTR1-5) to exert numerous effects. A gene product related SST, cortistatin (CST), also interacts with SSTR1-5. Here we have investigated regulation SSTR1-5 CST SST knockout (SSTKO) mice. SSTRs were quantitated individually by subtype-selective binding analysis, immunocytochemistry, mRNA measurement showed, SSTKO mice, up-regulation subtypes 1, 2, 4, 5, down-regulation...

The diabetic heart switches to exclusively using fatty acid (FA) for energy supply and does so by multiple mechanisms including hydrolysis of lipoproteins lipoprotein lipase (LPL) positioned at the vascular lumen. We determined mechanism that leads an increase in LPL after diabetes. Diazoxide (DZ), agent decreases insulin secretion causes hyperglycemia, induced a substantial activity This paralleled robust phosphorylation Hsp25, decreasing its association with PKCdelta, allowing this protein...

Abstract The hypothalamus is a major site of somatostatin (SST) production and action. SST synthesized in several hypothalamic nuclei involved variety functions. Using receptor (SSTR)‐specific antibodies, we localized SSTR subtypes the rat hypothalamus. In addition, also demonstrated SSTRs colocalization with SST, NADPH‐diaphorase (NADPH‐d), tyrosine hydroxylase (TH). SSTR1 strongly neurons all as well nerve fibers zona externa median eminence ependyma third ventricle. SSTR2 expressed most...