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

Radioligand binding and functional assays were employed to demonstrate the existence of somatostatin receptors in the murine neuroblastoma clone N1E-115. Saturation experiments with [125I][Tyr11]somatostatin-14 indicated the presence of a single class of binding sites in membranes prepared from N1E-115 cells (Kd = 83 pM; Bmax = 21,000 receptors/cell). Somatostatin-14, somatostatin-28 and L363586 (cyclo(N-Me-ALA-TYR-D-TRP-LYS-VAL-PHE] all displaced the 125I-ligand monophasically in N1E-115 cells (Ki values were 28, 82 and 34 pM, respectively), which contrasted with the binding heterogeneity apparent with L363586 in rat brain membranes. The binding of [125I][Tyr11]somatostatin-14 was reduced by GppNHp, indicating that N1E-115 somatostatin receptors interacted with guanine nucleotide binding protein(s). Somatostatin agonists decreased by 30-50% the levels of [3H]cyclic AMP induced in intact cells by forskolin, prostaglandin E1, or vasoactive intestinal polypeptide. The EC50 values for inhibition of the [3H]cyclic AMP response to PGE1 by L363586, somatostatin-14, and somatostatin-28 were 0.24, 0.63 and 1.0 nM, respectively. Pertussis toxin treatment of N1E-115 cells reduced both binding to the receptor and the functional response to somatostatin-14. These data suggest that a single class of somatostatin receptors in N1E-115 cells are linked to the inhibition of adenylate cyclase through a Gi protein.
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PMID:Biochemical evidence for somatostatin receptors in murine neuroblastoma clone N1E-115. 256 62

The pathways by which islet B, A, and D cells bind and internalize homologous (self) and heterologous (other) islet hormones were compared. [125I-Tyr]Somatostatin-14 (S-14), 125I-insulin, and 125I-glucagon were incubated with monolayer cultures of neonatal rat islet cells. Tissues were processed for quantitative electron microscopic autoradiography by the probability circle method coupled to morphometry. For all three radioligands and all three cell types surface labeling was rapidly followed by internalization of the radioligands into endocytotic vesicles. The further intracellular movement of the ligand occurred in a time- and temperature-related manner and depended on whether it was homologous or heterologous for the cell in question. Thus [125I-Tyr]S-14 in B and A cells, 125I-insulin in A and D cells, and 125I-glucagon in B and D cells were rapidly transferred from endocytotic vesicles to lysosomal structures. By contrast, [125I-Tyr]S-14 in D cells, 125I-insulin in B cells, and 125I-glucagon in A cells showed poor progression from endocytotic vesicles to downstream vesicular structures. We conclude that (a) each of the three radioligands is internalized by islet cells in a time- and temperature-dependent manner; (b) after initial internalization the further intracellular progression of the endocytosed radioligand occurs freely in cells heterologous for the radioligand but poorly in cells homologous for the radioligand; and (c) binding and endocytosis can be uncoupled from lysosomal degradation of ligand.
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PMID:Binding and internalization of somatostatin, insulin, and glucagon by cultured rat islet cells. 256 74

Cyclic-disulfide-containing analogues of somatostatin, Xaa1-Cys2-Xaa3-DTrp4-Lys6-Thr5-Xaa7- Xaa8 [Xaa1 = H or DPhe; Xaa3 = Phe or Tyr; Xaa7 = Cys, Me2Cys or Me2DCys; Xaa8 = OH, Thr8 (OH) or Thr8NH2], were examined in aqueous solution by 1H-NMR spectroscopy and circular dichroism. The influence of the helical nature of the disulfide bridge and the presence of exocyclic residues on biological activity were investigated with particular care.
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PMID:Conformation of two somatostatin analogues in aqueous solution. Study by NMR methods and circular dichroism. 257 30

The gastroenteropancreatic (GEP) endocrine system of three reptiles, Testudo graeca, Mauremys caspica, and Lacerta lepida, was investigated by means of immunocytochemistry. Single and double immunostaining methods have demonstrated immunoreactivity for insulin, glucagon, pancreatic polypeptide (PP), somatostatin, serotonin, and peptide tyrosine tyrosine (PYY) in endocrine cells of the pancreas of the reptiles studied. Islet-like structures with insulin-immunoreactive (IR) cells surrounded by glucagon-IR cells were observed only in the splenic portion of the pancreas of M. caspica. Occasionally, somatostatin- and PP-IR cells were associated with glucagon-containing cells. Endocrine cells were also observed in the excretory ducts of the exocrine glands. Serotonin, bombesin, neurotensin, gastrin, glucagon, somatostatin, PYY, and insulin were demonstrated immunocytochemically in open-type GEP cells of the digestive tract of the animals studied. Serotonin, somatostatin, and glucagon-immunoreactive cells were the most abundant endocrine cell types. In L. lepida, PP- and peptide tyrosine tyrosine-immunoreactive cells were also frequently observed. Cells containing cholecystokinin, gastric inhibitory peptide, met- and leu-enkephalin, motilin, secretin, and vasoactive intestinal peptide could not be detected. The present work demonstrates that the reptilian GEP endocrine system is a complex structure containing most of the regulatory peptides similar in structure to those found in higher vertebrates.
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PMID:Comparative immunohistochemical study of the gastroenteropancreatic endocrine system of three reptiles. 257 25

In order to determine the central or peripheral origin of the starvation-induced modifications of growth hormone (GH) and thyroid-stimulating hormone (TSH) secretions, the effects of starvation were studied in freely moving male rats with hypothalamo-hypophyseal disconnection. Five days after the disconnection GH secretion exhibited lower maximal values and higher trough levels and ultradian pulsatile secretion was lost as compared to controls. TSH levels were also decreased. The lesion did not modify pituitary somatostatin (SRIF) receptors as assessed by 125I-Tyr-O-D-Trp-8-SRIF binding or inhibition of adenylate cyclase activity. On the other hand, the growth hormone releasing factor (GRF) capacity to stimulate adenylate cyclase was strongly reduced by the lesion without modification of the affinity. Exposure to 72 h food deprivation decreased GH pulses and TSH levels in control rats but did not modify GH secretory profiles or TSH levels of lesioned rats. Plasma glucose and insulin levels were equally decreased after fasting in control and lesioned rats. Altogether, our results demonstrate that starvation-induced modifications of GH and TSH secretions are of central origin while glucose and insulin changes are peripherally triggered. They suggest that the hypothalamus is the only source of SRIF implicated in this effect.
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PMID:Involvement of central somatostatin in the alteration of GH secretion in starved rats. 257 76

A series of heptapeptide somatostatin (SRIF) analogs containing mercaptopropionic acid (Mpa) and based on the parent structure Mpa-Tyr-[D]Trp-Lys-Val-Cys-Thr-NH2 were synthesized by solid-phase methodologies and assayed for their effects on rat growth hormone (GH) secretion and their ability to displace [125I]Tyr11-SRIF bound to various tissues in vitro. Structural modifications consisted primarily of aromatic substitutions for Thr. All analogs were less potent than SRIF in inhibiting GH secretion in vitro from 4-day primary cultures of rat pituitary cells (0.04-21% that of SRIF). Higher GH inhibitory potencies were observed in an acute 15 min in vivo potency assay probably reflecting increases in plasma half-life of the analogs as compared to native SRIF. All analogs had extremely low binding affinity for rat cerebral cortex (0.05-4% that of SRIF), while binding potency for rat pancreas ranged from 3-130% of SRIF. Several analogs exhibited enhanced binding to human small cell lung carcinoma cells (SCLC; NCI-H69) as compared to SRIF. One of these, containing Phe at the C-terminus, exhibited an affinity 3.5 X greater than SRIF itself and was further tested for possible effects on the proliferation of SCLC and rat pancreatic tumor cells (AR42J) in vitro. The proliferation of both tumor types was inhibited 32 and 60%, respectively (p less than 0.01). The data suggest that SRIF and certain analogs may have a direct action on proliferating tumors independent of endocrine effects and that the anti-tumor activity of SRIF analogs can be further dissociated from the other actions of native SRIF, thereby providing for potentially more selective therapeutic analogs.
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PMID:Novel heptapeptide somatostatin analog displays anti-tumor activity independent of effects on growth hormone secretion. 257 97

1. NPY is a 36 amino acid tyrosine-rich peptide. It is one of the most abundant and widely distributed neuropeptides known today within the central nervous system with particularly high concentrations in the hypothalamus and in several limbic regions. 2. NPY seems to coexist with other on neurotransmitters like somatostatin, galanin, GABA and the catecholamines noradrenaline and adrenaline in discrete brain regions. 3. NPY binding sites are widely distributed in the brain. However they do not always overlap with the distribution of NPY-like immunoreactivity. 4. NPY is suggested to be involved in a large number of neuroendocrine functions, stress responses, circadian rhythms, central autonomic functions, eating and drinking behaviour, and sexual and motor behaviour. 5. Psychotropic drugs and neurotoxins can alter the NPY concentrations in discrete brain regions. 6. It is possible that NPY is related to various neurological and psychiatric illnesses, like Huntington's chorea, Alzheimer's disease, Parkinson's disease, eating disorders, and major depressive illness.
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PMID:Neuropeptide Y (NPY) and the central nervous system: distribution effects and possible relationship to neurological and psychiatric disorders. 266 85

The cytoprotective effect of a highly potent somatostatin (SRIF) analog, RC-121 (H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2), was examined in the absolute ethanol-induced gastric erosion model in rat. This analog diminished the degree of gastric erosion by 50-55% when administered in i.p. doses of 2 x 10(-10)-10(-8) g/100 g body weight, or in oral doses of 10(-8)-2 x 10(-7) g/100 body weight. The orally active, highly potent SRIF analogs may be useful as therapeutic agents in the treatment of human peptic ulcer.
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PMID:Protective effect of an orally administered, highly potent somatostatin analog (RC-121) against absolute ethanol-induced hemorrhagic erosions of the rat gastric mucosa. 273 41

As shown by an increase in plasma corticosterone concentrations, adenosine administration stimulated pituitary-adrenocortical activity. This effect was prevented by dexamethasone (2 mg/kg i.p.). Added in vitro, adenosine reduced both adrenal basal and adrenocorticotropic hormone (ACTH)-stimulated corticosterone release, while it stimulated pituitary ACTH release. This ACTH response was blocked by dexamethasone but not by Tyr-somatostatin. Restraint stress increased adenosine content in the anterior pituitary, suggesting its possible involvement in hormonal stress response. Because the effect of adenosine on plasma corticosterone was still present in rats with a pharmacological block of the endogenous corticotropin-releasing factor release, we propose that adenosine is involved in the regulation of adrenocortical secretion at the level of the anterior pituitary and that this role is exerted through an interaction with a stimulatory adenosine receptor.
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PMID:Adenosine and pituitary-adrenocortical axis activity in the rat. 281 76

1. Intracellular recordings of membrane potential and current were made from neurones in the lateral parabrachial nucleus in slices of rat brain in vitro. 2. The membrane was hyperpolarized by the opioid peptides Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL, 0.01-1 microM) and [Met5]enkephalin (3-30 microM), though not by Tyr-D-Pen-Gly-Phe-D-Pen and U50488. In two experiments, naloxone competitively antagonized the effects of DAGOL and [Met]enkephalin with equilibrium dissociation constants of 0.8 and 3.2 nM, respectively. 3. Baclofen (0.3-30 microM) also hyperpolarized the neurones; this action was unaffected by naloxone. 4. DAGOL, [Met5]enkephalin and baclofen caused outward currents at the resting potential. These currents reversed polarity at a membrane potential which changed with the logarithm of the extracellular potassium concentration. 5. Muscarine has been shown previously to increase the potassium conductance by an action at M2-receptors: the potassium currents induced by maximal concentrations of muscarine, baclofen and [Met5]enkephalin were non-additive, indicating that these agonists opened the same population of potassium channels. 6. Noradrenaline, UK14304, carboxamidotryptamine, dopamine, adenosine and somatostatin had little or no effect on membrane potential. 7. It is concluded that rat lateral parabrachial neurones express mu-opioid, gamma-aminobutyric acidB (GABAB), and M2-muscarinic receptors: activation of any of these receptors increases the potassium conductance of the membrane and inhibits the neurones through hyperpolarization.
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PMID:Agonists at mu-opioid, M2-muscarinic and GABAB-receptors increase the same potassium conductance in rat lateral parabrachial neurones. 285 64


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