Comparative changes in breast cancer cell proliferation and signalling following somatostatin and cannabidiol treatment.

Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related death among women worldwide. Somatostatin (SST) and Cannabinoids have an anti-proliferative and pro-apoptotic effect, but the mechanisms of their actions remain elusive. In the present study, we have evaluated the effects of SST, Cannabidiol (CBD) alone or in combination on receptor expression, cell proliferation and apoptosis and related downstream signalling pathways in MDA-MB-231 and MCF-7 breast cancer cells.

Somatostatin-Mediated Regulation of Retinoic Acid-Induced Differentiation of SH-SY5Y Cells: Neurotransmitters Phenotype Characterization.

During brain development, neurite formation plays a critical role in neuronal communication and cognitive function. In the present study, we compared developmental changes in the expression of crucial markers that govern the functional activity of neurons, including somatostatin (SST), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), brain nitric oxide synthase (bNOS), gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD-65) and synaptic vesicle protein synaptophysin (SYP) in non-differentiated and retinoic acid (RA)-induced differentiated SH-SY5Y cells. We further determined the role of SST in regulating subcellular distribution and expression of neurotransmitters.

Cannabinol modulates neuroprotection and intraocular pressure: A potential multi-target therapeutic intervention for glaucoma.

Objectives: Glaucoma is characterized by progressive damage of the retinal ganglion cells (RGCs), resulting in irreversible vision loss. Cannabinoids (CBs) ameliorate several factors that contribute to the progression of glaucoma, including increased intraocular pressure (IOP), degeneration of RGC and optical nerve (ON) damage. However, a direct correlation of specific CBs with the molecular events pertaining to glaucoma pathology is not well established.

Somatostatin Ameliorates β-Amyloid-Induced Cytotoxicity via the Regulation of CRMP2 Phosphorylation and Calcium Homeostasis in SH-SY5Y Cells.

Somatostatin is involved in the regulation of multiple signaling pathways and affords neuroprotection in response to neurotoxins. In the present study, we investigated the role of Somatostatin-14 (SST) in cell viability and the regulation of phosphorylation of Collapsin Response Mediator Protein 2 (CRMP2) (Ser522) via the blockade of Ca accumulation, along with the inhibition of cyclin-dependent kinase 5 (CDK5) and Calpain activation in differentiated SH-SY5Y cells. Cell Viability and Caspase 3/7 assays suggest that the presence of SST ameliorates mitochondrial stability and cell survival pathways while augmenting pro-apoptotic pathways activated by Aβ.

Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism.

Purpose: Propylthiouracil (PTU)-induced hypothyroidism is a well-established model for assessing hormonal and morphological changes in thyroid as well as other central and peripheral tissues. Somatostatin (SST) is known to regulate hormonal secretion and synthesis in endocrine tissues; however, nothing is currently known about the distribution of SST and its receptor in hypothyroidism.

Method: In the present study, the comparative immunohistochemical distribution of SST and somatostatin receptors (SSTRs) were analyzed in PTU-induced hypothyroid rats.

Somatostatin-Mediated Changes in Microtubule-Associated Proteins and Retinoic Acid-Induced Neurite Outgrowth in SH-SY5Y Cells.

Somatostatin (SST) is a growth hormone inhibitory peptide involved in regulation of several physiological responses of cells including neurotransmission, cell migration, maturation, and neurite formation. In the present study, we examined the role of SST in all-trans retinoic acid (RA)-induced progression of neurite outgrowth in SH-SY5Y cells. We also determined the morphological and developmental changes in prominent intracellular markers of neurite growth including microtubule-associated protein 2 (MAP2), neuron-specific III β-tubulin (TUJ1), and Tau.

Somatostatin Maintains Permeability and Integrity of Blood-Brain Barrier in β-Amyloid Induced Toxicity.

In Alzheimer's disease (AD), the impaired clearance of β-amyloid peptide (Aβ) due to disrupted tight junction and transporter proteins is the prominent cause of disease progression. Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss. However, the role of SST in preservation of blood-brain barrier (BBB) integrity and functionality in Aβ-induced toxicity is not known.

Characterization of somatostatin receptors and associated signaling pathways in pancreas of R6/2 transgenic mice.

The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (β), glucagon (α) and somatostatin (δ) producing cells in the pancreatic islets of 11weeks old R6/2 Huntington's Disease transgenic (HD tg) and age-matched wild type (wt) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptophysin (SYP) in addition to signal transduction pathways associated with diabetes. In R6/2 mice, islets are relatively smaller in size, exhibit enhanced expression and nuclear inclusion of mHtt along with the loss of insulin, glucagon and somatostatin expression.

Regional and subcellular distribution of GABA ρ3 receptor in brain of R6/2 mouse model of Huntington's disease.

In the present study, we describe the distribution of GABA ρ3 receptor immunoreactivity in the cortex, striatum and hippocampus of wild type (wt) and 11 weeks old HD transgenic (tg) R6/2 mouse brain. In the brain of wt mice, GABA ρ3 immunoreactivity is well expressed in neuronal cells, nerve fibers and axonal processes. In comparison to wt, GABA ρ3 receptor like immunoreactivity decreases significantly in all three brain regions of R6/2 mice.

Somatostatin receptor 5 is a prominent regulator of signaling pathways in cells with coexpression of Cannabinoid receptors 1.

Endocannabinoids and somatostatin (SST) play critical roles in several pathophysiological conditions via binding to different receptor subtypes. Cannabinoid receptor 1 (CB1R) and somatostatin receptors (SSTRs) are expressed in several brain regions and share overlapping functions. Whether these two prominent members of G-protein-coupled receptor (GPCR) family interact with each other and constitute a functional receptor complex is not known.

Colocalization of cannabinoid receptor 1 with somatostatin and neuronal nitric oxide synthase in rat brain hypothalamus.

Despite several overlapping functions of cannabinoid receptor 1 (CB1 receptor), somatostatin (SST), and neuronal nitric oxide synthase (nNOS) in the hypothalamus, nothing is currently known whether CB1 receptor-positive neurons coexpress SST and nNOS. In the present study, we describe the colocalization of CB1 receptor with SST and nNOS in the rat brain hypothalamus. In the hypothalamus, the distributional patterns and colocalization of CB1 receptor with SST and nNOS were selective and region specific.

Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity.

Objectives: The expression of GABA(A) receptors and the effects of GABAA receptor agonists on the response properties of tongue afferent fibres were investigated in female rats to determine if peripheral GABA receptors might be a target of topical benzodiazepines when used for pain relief in burning mouth syndrome patients.

Design: Nerve fibres in tongue sections from six female rats were identified using protein gene product 9.5, and the co-expression of the γ subunit of GABAA receptor and substance P assessed in the nerve fibres.

δ-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling.

Pain relief is the principal action of opioids. Somatostatin (SST), a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 (SSTR4).

Somatostatin receptor-2 negatively regulates β-adrenergic receptor mediated Ca(2+) dependent signaling pathways in H9c2 cells.

In the present study, we report that somatostatin receptor 2 (SSTR2) plays a crucial role in modulation of β1AR and β2AR mediated signaling pathways that are associated with increased intracellular Ca(2+) and cardiac complications. In H9c2 cells, SSTR2 colocalizes with β1AR or β2AR in receptor specific manner. SSTR2 selective agonist inhibits isoproterenol and formoterol stimulated cAMP formation and PKA phosphorylation in concentration dependent manner.

Nitric oxide release from trigeminal satellite glial cells is attenuated by glial modulators and glutamate.

Nitric oxide (NO) is suggested to play an important role in primary headaches. It has been proposed that release of NO from satellite glial cells (SGCs) of the trigeminal ganglion (TG) could contribute to the pathogenesis of these headaches. The principal aim of this study was to investigate if the phosphodiesterase inhibitor Ibudilast (Ibu) and 1α,25-dihydroxyvitamin D3 (Vit D3) could interfere with NO release from trigeminal SGCs.

Somatostatin preserved blood brain barrier against cytokine induced alterations: possible role in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurological disorder associated with demyelination, impaired blood brain barrier (BBB), axonal damage and neuronal loss. In the present study, we measured somatostatin (SST) and tumor necrosis factor-α (TNF-α) like immunoreactivity in CSF samples from MS and non-MS patients. We also examined the role of SST in cytokines and lipopolysaccharide (LPS)-induced damage to the BBB using human brain endothelial cells in culture.

Interaction of structure-specific and promiscuous G-protein-coupled receptors mediates small-molecule signaling in Caenorhabditis elegans.

A chemically diverse family of small-molecule signals, the ascarosides, control developmental diapause (dauer), olfactory learning, and social behaviors of the nematode model organism, Caenorhabditis elegans. The ascarosides act upstream of conserved signaling pathways, including the insulin, TGF-β, serotonin, and guanylyl cyclase pathways; however, the sensory processes underlying ascaroside function are poorly understood. Because ascarosides often are multifunctional and show strongly synergistic effects, characterization of their receptors will be essential for understanding ascaroside biology and may provide insight into molecular mechanisms that produce synergistic outcomes in small-molecule sensing.

Isoproterenol induced hypertrophy and associated signaling pathways are modulated by somatostatin in H9c2 cells.

Background: Somatostatin (SST), a growth hormone inhibitory peptide plays key role in regulation of cell proliferation via modulation of mitogen activated protein kinases (MAPKs) and cell survival pathway. In cardiac physiology, β-Adrenergic receptors (β-ARs) play crucial role in regulation of downstream signaling pathways in receptor specific manner. The aim of the current study was to delineate the mechanistic insight for the role of SST on β-AR mediated signaling which promotes hypertrophy and apoptosis in rat fetal cardiomyocytes (H9c2 cells).

Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on Somatostatin Receptors.

G-protein coupled receptors (GPCRs) are cell surface proteins responsible for translating >80% of extracellular reception to intracellular signals. The extracellular information in the form of neurotransmitters, peptides, ions, odorants etc is converted to intracellular signals via a wide variety of effector molecules activating distinct downstream signaling pathways. All GPCRs share common structural features including an extracellular N-terminal, seven-transmembrane domains (TMs) linked by extracellular/intracellular loops and the C-terminal tail.

Heterodimerization of β2 adrenergic receptor and somatostatin receptor 5: Implications in modulation of signaling pathway.

Background: In the present study, we describe heterodimerization between human-Somatostatin Receptor 5 (hSSTR5) and β2-Adrenergic Receptor (β2AR) and its impact on the receptor trafficking, coupling to adenylyl cyclase and signaling including mitogen activated protein kinases and calcineurin-NFAT pathways.

Methods: We used co-immunoprecipitation, photobleaching- fluorescence resonance energy transfer and Fluorescence assisted cell sorting analysis to characterize heterodimerization between SSTR5 and β2AR.

Results: Our results indicate that hSSTR5/β2AR exist as preformed heterodimers in the basal condition which is enhanced upon co-activation of both receptors.

Role of somatostatin receptor 1 and 5 on epidermal growth factor receptor mediated signaling.

Epidermal growth factor (EGF) regulates normal and tumor cell proliferation via epidermal growth factor receptor (EGFR) phosphorylation, homo- or heterodimerization and activation of mitogen-activated protein kinases (MAPKs) and PI3K/AKT cell survival pathways. In contrast, SST via activation of five different receptor subtypes inhibits cell proliferation and has been potential target in tumor treatment. To gain further insight for the effect of SSTRs on EGFR activated signaling, we determine the role of SSTR1 and SSTR1/5 in human embryonic kidney (HEK) 293 cells.

Receptor specific crosstalk and modulation of signaling upon heterodimerization between β1-adrenergic receptor and somatostatin receptor-5.

In the present study we describe heterodimerization, trafficking, coupling to adenylyl cyclase and signaling in HEK-293 cells cotransfected with human-somatostatin receptor 5 (hSSTR5) and β(1)-adrenergic receptor (β(1)AR). hSSTR5/β(1)AR exists as heterodimers in basal conditions which was further enhanced upon synergistic activation of both receptors. Activation of either β(1)AR or hSSTR5 displayed dissociation of heterodimerization.

Somatostatin receptor-3 mediated intracellular signaling and apoptosis is regulated by its cytoplasmic terminal.

In the present study, we describe the role of cytoplasmic terminal (C-tail) domain in regulating coupling to adenylyl cyclase, signaling, and apoptosis in human embryonic kidney (HEK-293) cells transfected with wild type (wt)-hSSTR3 and C-tail deleted mutants. Cells transfected with wt-hSSTR3 and C-tail mutants show comparable membrane expression; however, display decreased expression in presence of agonist. wt-hSSTR3 exists as preformed homodimer at cell surface in basal conditions and decreases in response to agonist.

Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways.

Epidermal growth factor through the stimulation of epidermal growth factor receptor (EGFR) plays a critical role in the activation of MAPKs and phosphatidylinositol-3-protein kinase/AKT cell survival pathways attributed in many pathological conditions. At the cellular level, such functions involve EGFR overactivation and phosphorylation. In the present study, we describe that human embryonic kidney-293 cells transfected with somatostatin (SST) receptor 5 (SSTR5) exhibit inhibition of EGFR phosphorylation and modulate MAPK and phosphatidylinositol-3-protein kinase/AKT cell survival signaling.

SD-8, a novel therapeutic agent active against multidrug-resistant Gram positive cocci.

Anti-bacterial drug resistance is one of the most critical concerns among the scientist worldwide. The novel antimicrobial decapeptide SD-8 is designed and its minimal inhibitory concentration and therapeutic index (TI) was found in the range of 1-8 μg/ml and 45-360, respectively, against major group of Gram positive pathogens (GPP). The peptide was also found to be least hemolytic at a concentration of 180 μg/ml, i.