Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple neurotransmitter systems are affected in senile dementia of the Alzheimer's type (SDAT). Among them, acetylcholine has been most studied. It is now well accepted that the activity of the enzyme, choline acetyltransferase (ChAT) is much decreased in various brain regions including the frontal and temporal cortices, hippocampus and nucleus basalis of Meynert (nbm) in SDAT. Cortical M2-muscarinic and nicotinic cholinergic receptors are also decreased but only in a certain proportion (30-40%) of SDAT patients. For other systems, it appears that cortical serotonin (5-HT)-type 2 receptor binding sites are decreased in SDAT. This diminution in 5-HT2 receptors correlates well with the decreased levels of somatostatin-like immunoreactive materials found in the cortex of SDAT patients. Cortical somatostatin receptor binding sites are decreased in about one third of SDAT patients. Finally, neuropeptide Y and neuropeptide Y receptor binding sites are distributed in areas enriched in cholinergic cell bodies and nerve fiber terminals and it would be of interest to determine possible involvement of this peptide in SDAT. Thus, it appears that multi-drug clinical trials should be considered for the treatment of SDAT.
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PMID:Neurotransmitter and receptor deficits in senile dementia of the Alzheimer type. 287 14

The diverse physiological effects of somatostatin are mediated by a family of cell surface receptors that bind somatostatin selectively and with high affinity. The somatostatin receptors are members of the seven transmembrane segment receptor superfamily and molecular cloning studies have identified five types, designated sstr1-5. The human somatostatin receptors vary in size from 364 (sstr5) to 418 (sstr3) amino acids with 46-61% amino acid identity between receptors, and 105 amino acids are invariant. The sequences of the seven putative alpha-helical membrane-spanning domains are more highly conserved than those of the extracellular N- and intracellular C-terminal domains. Two forms of sstr2 have been identified in the mouse, sstr2A and sstr2B, which differ in size and sequence of the intracellular C-terminal domain. These two forms of sstr2 are products of a common gene and are generated by alternative splicing with sstr2A and sstr2B being the products of the unspliced and spliced forms, respectively, of sstr2 mRNA. Thus, functional diversity within the somatostatin receptor family may result from the expression of multiple types as well as from alternative splicing. The five somatostatin receptors have distinct patterns of expression in the central nervous system and peripheral tissues. They have also been expressed in vitro and shown to have different pharmacological properties. Somatostatin analogues selective for sstr2, sstr3 and sstr5 have been identified which will facilitate in vivo studies of the functions of these somatostatin receptors. Such studies to date suggest that sstr2 mediates inhibition of growth hormone secretion and sstr5 mediates inhibition of insulin secretion. The molecular cloning and functional characterization of the somatostatin receptor family is a first step in elucidating the diverse effects of somatostatin on cellular functions.
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PMID:Molecular biology of somatostatin receptors. 758 53

Guinea-pig neuropeptide Y1 and rat pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells were internalized rapidly upon attachment of selective peptide agonists. The Y1 and Y2, but not the Y4, receptor also internalized the nonselective neuropeptide Y receptor agonist, human/rat neuropeptide Y. The internalization of guinea-pig neuropeptide Y2 receptor expressed in Chinese hamster ovary cells was small at 37 degrees C, and essentially absent at or below 15 degrees C, possibly in connection to the large molecular size of the receptor-ligand complexes (up to 400 kDa for the internalized fraction). The rate of intake was strongly temperature dependent, with essentially no internalization at 6 degrees C for any receptor. Internalized receptors were largely associated with light, endosome-like particulates. Sucrose dose-dependently decreased the internalization rate for all receptors, while affecting ligand attachment to cell membrane sites much less. Internalization of the Y1 and the Y4 receptors could be blocked, and that of the Y2 receptor significantly inhibited, by phenylarsine oxide, which also unmasked spare cell-surface receptors especially abundant for the Y2 subtype. The restoration of Y1 and Y4 receptors after agonist peptide pretreatment was decreased significantly by cycloheximide and monensin. Thus, in Chinese hamster ovary cells the Y1 and Y4 receptors have much larger subcellular dynamics than the Y2 receptor. This differential could also hold in organismic systems, and is comparable with the known differences in internalization of angiotensin, bradykinin, somatostatin and opioid receptor subtypes.
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PMID:Cloned neuropeptide Y (NPY) Y1 and pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells show considerable agonist-driven internalization, in contrast to the NPY Y2 receptor. 1117 53

Obesity is a major public health concern and environmental factors are involved in its development. The hypothalamus is a primary site for the integration of signals for the regulation of energy homeostasis. Dysregulation of these pathways can lead to weight loss or gain. Some drugs in development can have favourable effects on body weight, acting on some of these pathways and leading to responses resulting in weight loss. Strategies for the management of weight reduction include exercise, diet, behavioural therapy, drug therapy and surgery. Investigational antiobesity medications can modulate energy homeostasis by stimulating catabolic or inhibiting anabolic pathways. Investigational drugs stimulating catabolic pathways consist of leptin, agonists of melanocortin receptor-4, 5-HT and dopamine; bupropion, growth hormone fragments, cholecystokinin subtype 1 receptor agonist, peptide YY3-36, oxyntomodulin, ciliary neurotrophic factor analogue, beta3-adrenergic receptor agonists, adiponectin derivatives and glucagon-like peptide-1. On the other hand, investigational drugs inhibiting anabolic pathways consist of the ghrelin receptor, neuropeptide Y receptor and melanin-concentrating hormone-1 antagonists; somatostatin analogues, peroxisome proliferator-activated receptor-gamma and -beta/delta antagonists, gastric emptying retardation agents, pancreatic lipase inhibitors, topiramate and cannabinoid-1 receptor antagonists. These differing approaches are reviewed and commented on in this article.
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PMID:Investigational therapies in the treatment of obesity. 1685 93

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors, mainly localized in the gastrointestinal system. What characterizes NENs is the expression of hormone receptors on the tumor cell surface, making them accessible for diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Somatostatin receptors subtype-two (SST2) play an important role in NENs since they are overexpressed and homogeneously distributed at the surface of the majority of NENs. Accordingly, targeting SST2 for diagnostic and therapeutic purposes has been established. Current research aims at upregulating its expression by epigenetic treatment or improving its targeting via use of alternative radioligands. In addition, recent data suggest a future role of SST antagonists as a diagnostic tool and a potential therapeutic option. Another promising target is the glucagon-like peptide-1 (GLP-1) receptor. Targeting GLP-1R using exendin-4 (GLP-1 analogue) has a high sensitivity for the localization of the often SST2-negative sporadic insulinomas and insulinomas in the context of multiple endocrine neoplasia type-1. Further options for patients with insufficient expression of SST2 involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4), which have been evaluated for potential theranostic approach in symptomatic NENs or dedifferentiated tumors. Recently, new targets such as the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs. Finally, minigastrin - a ligand targeting the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut neuroendocrine tumors - may improve future management of these diseases with currently limited therapeutic options. This review summarises the current approaches and future challenges of diagnostic and therapeutic evaluations in neuroendocrine neoplasms.
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PMID:Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges. 3249 50