[Show abstract][Hide abstract] ABSTRACT: Somatostatin receptors are an important target for medical treatment of pituitary and neuroendocrine tumors. To date, five somatostatin receptor (sst) subtypes have been identified. The currently available somatostatin analogues octreotide and lanreotide have predominantly affinity for sst. Pasireotide is a sst multireceptor ligand with affinity for sst, sst, sst and sst and this broader binding profile may translate into a higher efficacy with respect to suppression of hormone production and cell growth in certain tumors. Experimental animal studies and in vitro studies with cultured tumor cells have shown that pasireotide strongly suppresses growth hormone and adrenocorticotropin production. In addition, pasireotide can influence tumor cell growth via effects on apoptosis and angiogenesis. In this review, the role of somatostatin receptors in pituitary and neuroendocrine tumors is briefly discussed followed by an overview of possible applications of pasireotide based on recent trials in patients with acromegaly, Cushing's disease and neuroendocrine tumors.
[Show abstract][Hide abstract] ABSTRACT: RATIONALE: Extrapyramidal motor signs are the major features of Parkinson's disease (PD). It is unclear whether there is a link between these signs and such PD-associated factors as brain somatostatin deficiency and aging. OBJECTIVES: This study aimed to examine whether an inhibition of the brain somatostatin system can initiate catalepsy, a model of extrapyramidal disorders, in young and aged rats. METHODS: The animals of 100-110 and 540-560 days of age were used. Catalepsy was measured using the bar test. The inhibition of the brain somatostatin activity was simulated by intracerebroventricular administration of a somatostatin antagonist, cyclosomatostatin. RESULTS: Cyclosomatostatin dose-dependently induced catalepsy in aged, but not in young rats. The cataleptic response was reversed by a somatostatin analog, octreotide. CONCLUSIONS: The combination of aging and brain somatostatin deficiency can lead to catalepsy in rats. Since both factors are frequently observed in PD patients, the present results might be of relevance for pathogenesis of extrapyramidal signs in this disease.
[Show abstract][Hide abstract] ABSTRACT: The biological actions of somatostatin are mediated by a family of five G protein-coupled receptors (GPCRs), named sst1 through sst5 . Somatostatin receptors exhibit equally high binding affinities to their natural ligand SS-14 and largely overlapping distributions. The overexpression of somatostatin receptors in human tumors is the molecular basis for diagnostic and therapeutic application of the stable somatostatin analogs octreotide, lanreotide and pasireotide. The efficiency of somatostatin receptor signaling is tightly regulated and ultimately limited by the coordinated phosphorylation and dephosphorylation of intracellular carboxyl-terminal serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite-specific antibodies for human sst2 and sst5 receptors. These phosphosite-specific antibodies are unique tools to monitor the spatial and temporal dynamics of receptor phosphorylation and dephosphorylation. Using a combined approach of phosphosite-specific antibodies and small interfering RNA (siRNA) knockdown screening relevant kinases and phosphatases were identified. Emerging evidence suggests distinct mechanisms of agonist-selective fine-tuning for individual somatostatin receptors. The recently uncovered differences in phosphorylation and dephosphorylation of these receptors may hence be of physiological significance in mediating responses to acute, persistent or repeated stimuli in a variety of target tissues.
British Journal of Pharmacology 12/2013; · 5.07 Impact Factor
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