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)

The solubilization of somatostatin receptors from guinea-pig pancreas by different non-denaturing detergents was investigated after stabilization of the receptors by prior binding of 125I-[Tyr11]somatostatin or its analogue 125I-[Leu8,DTrp22,Tyr25]somatostatin 28, to pancreatic plasma membranes. The somatostatin-receptor complexes were solubilized in a high yield by Zwittergent 3-14 (3-[tetradecyldimethylammonio]-1-propanesulfonate), a zwitterionic detergent. Other detergents, digitonin, Triton X-100, Chaps (3-[cholamidopropyldimethylammonio]-1-propanesulfonate) and octyl beta-D-glycopyranoside, achieved only partial solubilization. The recovery of receptor complexes was increased by glycerol. In order to characterize solubilized somatostatin-receptor complexes, membranes receptors were covalently labelled using N-5-azido-2-nitrobenzoyloxysuccinimide as cross-linking reagent before solubilization. Gel filtration chromatography analysis resulted in the identification of a major protein component of apparent Mr = 93,000 which interacted with the two radioligands. In addition, a similar component of Mr = 88,000 was characterized after analysis by SDS-PAGE of membrane receptors covalently cross-linked with 125I-[Leu8,DTrp22,Tyr25]somatostatin 28 by different heterobifunctional reagents: N-5-azido-2-nitrobenzoyloxysuccinimide, N-hydroxysuccinimidyl 4-azidobenzoate, N-succinimidyl 6-(4'-azido-2'-nitrophenylamino)hexanoate. Optimal cross-linking results were obtained with N-5-azido-2-nitrobenzoyloxysuccinimide. The solubilized somatostatin-receptor complex was adsorbed to wheat-germ agglutinin-agarose column and eluted by specific sugars. We concluded that the guinea-pig pancreatic somatostatin receptor in the membrane and in the non-denaturing detergent solution behaves as a protein monomer of apparent Mr approximately 85,000-90,000. The somatostatin receptor is a glycoprotein which contains complex-type carbohydrate chains.
 ...
PMID:Solubilization and characterization of guinea-pig pancreatic somatostatin receptors. 303 26

Somatostatin receptors in the rat pituitary gland were characterized by binding analysis with a radioiodinated high affinity somatostatin analogue, 125I-Tyr1[D-Trp8]somatostatin. Receptor binding of this derivative reached equilibrium at 30 min and was maintained at a plateau for at least 60 min. Two L-Trp8- labeled somatostatin analogues. 125I-Tyr1- and [125I-Tyr11]somatostatin, displayed less stable and lower specific uptake and higher nonspecific binding. In contrast to the rapid degradation of the L-Trp8 ligands during binding assay, 125I-Tyr1]D-Trp8]somatostatin retained more than 80% of its binding activity after 90 min of incubation with pituitary particles. Pituitary particles bound 125I-Tyr1]D-Tyr8]somatostatin with high affinity (Ka = 8.6 +/- 1.2 X 10(9) M-1) and capacity of 54.4 +/- 2.6 fmol/mg. These binding sites showed specificity for the native peptide and its active analogues, and other peptide hormones, including angiotensin II, thyrotropin-releasing hormone, vasopressin, oxytocin, substance P, and gonadotropin-releasing hormone, did not inhibit tracer binding. A good correlation was observed between the binding affinities of several somatostatin analogues and their potencies as inhibitors of growth hormone release in rat pituitary cells. These findings emphasize the physiological importance of the pituitary somatostatin receptor in mediating the inhibitory action of the peptide on growth hormone release. The use of Tyr1[d-Trp8]somatostatin as a labeled ligand permits accurate determinations of the binding affinity and concentration of receptors for somatostatin in the normal pituitary gland and provides a basis for further studies of somatostatin receptor regulation and receptor-mediated cellular effects of the tetradecapeptide.
 ...
PMID:Pituitary somatostatin receptors. Characterization by binding with a nondegradable peptide analogue. 612 Jan 62

Using 32P-labeled histone as exogenous substrate, we showed a potent stimulatory effect of somatostatin on cytosolic phosphoprotein phosphatases (PPPases; phosphoprotein phosphohydrolase, EC 3.1.3.16) in rat gastric mucosal cells. Partial purification of cytosolic fraction in DEAE-Sephadex ion-exchange chromatography and further gel filtration on Sephadex C-75 and Sephadex G-100 separated somatostatin-dependent PPPases into three distinct molecular species. One corresponding to Mr 130,000 was devoid of any PPPase activity but specifically bound [Tyr1]somatostatin 125I-labeled on the Tyr ([125I-Tyr1]somatostatin) with an apparent equilibrium dissociation constant of 3 x 10(-10) M. The two other molecular species corresponded to Mrs 64,000 and 13,000. They produced catalytic dephosphorylation of 32P-labeled histone, but they were not sensitive to somatostatin and did not show any specific binding to radiolabeled hormone. Mixing of the larger with either of the two smaller molecular species resulted in concentration -dependent inhibition of PPPase activity. However this inhibition was reversed by increased concentrations of somatostatin, with the concentration for half-maximal reactivation on being close to 0.1 nM. Furthermore somatostatin stimulation in reconstituted materials developed according to a rapid time course (t1/2, less than 5 sec), consistent with that observed for binding of [125I-Tyr1]somatostatin. These results strongly argue for the presence of an intracellular somatostatin receptor in gastric mucosal cells and characterize this receptor as a PPPase regulatory subunit. Thus, substrate dephosphorylation could be the primary event triggering physiological effects of somatostatin in stomach and perhaps other organs of the digestive tract [Reyl, F. & Lewin, M. J.l M. (1981) Biochim. Biophys. Acta 675, 297-300].
 ...
PMID:Intracellular receptor for somatostatin in gastric mucosal cells: decomposition and reconstitution of somatostatin-stimulated phosphoprotein phosphatases. 612 13

Somatostatin binding to its receptors on rat pancreatic acinar membranes was characterized with [125I-Tyr1]somatostatin. Binding at 24 degrees C was rapid reaching a maximum after 60 min and was reversible upon the addition of 1 microM unlabeled ligand. Scatchard analysis revealed a single class of binding sites, with a Kd of 0.32 +/- 0.03 nM and a binding capacity of 600 +/- 54 fmol/mg of protein. Specificity for the somatostatin was demonstrated with the inhibition of labeled hormone binding by somatostatin analogs in proportion to their biological activities. When [125I-Tyr1]somatostatin was cross-linked to its receptors with the photoreactive cross-linker n-hydroxysuccinimidyl-4-azidobenzoate, the hormone was associated with Mr = 90,000 protein. Similar mobilities of the radioactive band were observed in the presence and absence of dithiothreitol. In contrast to other unrelated peptides, cholecystokinin (CCK) and its analogs directly reduced [125I-Tyr1] somatostatin binding to isolated membranes. The effect of CCK was one-half-maximal at 3 nM and maximal at 100 nM. In the presence of 3 nM CCK8, the binding capacity for somatostatin was decreased to 237 +/- 39 fmol/mg of protein without a significant change in affinity. Dibutyryl cyclic GMP, a CCK receptor antagonist, blocked this action of CCK8 indicating that the CCK receptor mediated the decrease in [125-Tyr1]somatostatin binding. In contrast cerebral cortex membranes, which also possess a somatostatin receptor, were not regulated by CCK. These results indicate, therefore, that 1) purified pancreatic acinar plasma membranes contain specific receptors for somatostatin, 2) the receptor has an apparent Mr of about 90,000, and 3) the binding of somatostatin to its receptor on pancreatic plasma membranes is regulated by CCK analogs acting via the CCK receptor.
 ...
PMID:The somatostatin receptor on isolated pancreatic acinar cell plasma membranes. Identification of subunit structure and direct regulation by cholecystokinin. 614 17

The binding characteristics of a stable somatostatin analogue, SMS 201-995, have been evaluated in a somatostatin receptor binding assay using [125I-Tyr11]somatostatin, and cortical, pituitary or pancreatic membranes. High affinity binding sites for somatostatin-14 and for SMS 201-995 were identified in rat cortex (Kd = 0.60 nM) as well as in pituitary (Kd = 0.74 nM) and pancreatic beta-cells (Kd = 0.18 nM). In the cortex, in contrary to the two other tissues, SMS 201-995 only labels a part (approximately 75%) of the receptors recognized by somatostatin-14. This suggests the presence in the cortex of more than one population of somatostatin receptors. In conclusion, SMS 201-995 appears as a valuable tool for differentiating the two somatostatin receptor types.
 ...
PMID:Evidence for two somatostatin-14 receptor types in rat brain cortex. 614 98

Granule fusion and the subsequent fission leading to hormone discharge are distinct and separable events in exocytosis. As an index of fusion, we followed the recruitment of granule-bound somatostatin receptors to the islet surface, an event which accompanies secretion vesicle migration and insulin secretion. Granule fission was monitored by measuring insulin release. Substitution of the impermeant salt sodium isethionate for NaCl led to a 90% decrease in glucose-stimulated insulin release with no inhibition of somatostatin receptor recruitment. The phenothiazine drugs, trifluoperazine and promethazine, believed to inhibit calcium-sensitive proteins involved with stimulus-secretion coupling blocked insulin release and somatostatin receptor recruitment in parallel. This suggests that these agents suppress intracellular events promoting fusion of the secretion granule with the plasma membrane. IBMX appears to stimulate specifically granule fission since IBMX-induced insulin release occurs acutely without an increase in somatostatin receptor recruitment. Sodium isethionate, which inhibits granule lysis, blocked IBMX-stimulated insulin release.
 ...
PMID:Granule fusion and fission (discharge) are biochemically dissociable events of exocytotic hormone release. 619 Feb 96

Eighty-seven percent of the total cellular pool of somatostatin (SRIF) receptors in pancreatic islets are located intracellularly. Upon glucose stimulation (300 mg/dl) of insulin release, 8-15% of intracellular SRIF receptors are translocated to the plasma membrane. Affinity of SRIF receptors does not change during their migration and the total cellular pool of receptors remains constant. With prolonged glucose stimulation, surface membrane somatostatin receptor concentration reaches a maximum level at 60 min.
 ...
PMID:Kinetics of somatostatin receptor migration in isolated pancreatic islets. 629 58

Somatostatin modulates both endocrine and exocrine functions in the gastric mucosa, where three of the five cloned somatostatin receptors are present. This study examines changes in somatostatin receptor (SSTR) mRNA abundance during fasting, feeding, and profound acid inhibition with omeprazole. Serum gastrin as well as somatostatin and SSTR mRNA abundances were measured in antrum and corpus. In Northern blots of corpus RNA, the SSTR2 probe hybridized with two previously reported species of mRNA (2.4 and 2.8 kb); in addition, a weak previously unreported 1.6-kb band was detected. In antrum, the 1.6-kb band dominated. Fasting increased antral somatostatin mRNA from 100 +/- 8 to 161 +/- 24% and SSTR mRNA from 100 +/- 10 to 179 +/- 14% (P < 0.05). Omeprazole reduced antral somatostatin mRNA to 34 +/- 4% of control (P < 0.05) and elevated SSTR mRNA to 135 +/- 5% of control (P < 0.01). Omeprazole treatment reduced corpus somatostatin mRNA to 59 +/- 5% (P < 0.05), and elevated SSTR mRNA to 140 +/- 3% of control (P < 0.01). The results therefore indicate that a novel SSTR mRNA subtype exists in the stomach and predominates in the antrum. The abundance of this SSTR mRNA is upregulated by both fasting and achlorhydria; conditions that increase or decrease endogenous antral somatostatin, respectively.
 ...
PMID:Differential expression and regulation of SSTR2 messenger RNA in rat gastric antrum and corpus. 748 6

In small-cell lung cancer (SCLC), CT scan remains the most accurate imaging modality for evaluating local extension and specific sites of metastatic disease. The role of nuclear medicine in the work-up of SCLC is still limited to the detection of bone metastases. Recently, a new potential diagnostic tool has been introduced based on the presence of somatostatin receptors in SCLC. With the use of radiolabelled somatostatin analogues it is hoped that an equally effective but simpler staging system has been found that gives a better separation of prognostic subgroups. This article reviews the role of nuclear medicine in general and somatostatin receptor scintigraphy in particular in the imaging and staging of SCLC. Clinical value in terms of sensitivity and specificity is discussed in relation with other imaging and staging modalities.
 ...
PMID:Imaging and staging of small-cell lung cancer: is there a future role for octreotide scintigraphy? 749 57

We have performed 100 scintigraphic investigations using [111In-diethylenetriaminepentaacetic acid-D-Phe1]octreotide (111In-octreotide) single photon emission tomography (SPECT) in patients with carcinoid tumors. One or several lesions could be detected in 77 cases, and true negative results were obtained in 11 cases. There were false-negative results in 12 cases compared with results from conventional radiological methods. The ratio between the SPECT signals from the area with the highest uptake and normal lung was used as a tumor:background ratio. An attenuation correction was made in all investigations. We found that lesions in untreated patients had lower tumor:background ratios compared with those in patients treated with somatostatin analogues (medians, 10 and 40, respectively; P < 0.001) or IFN (median, 23; P = 0.03). In untreated patients, there was a correlation between the tumor:background ratio and the levels of urinary 5-hydroxyindoleacetic acid (U-5HIAA) and p-chromogranin A. The data obtained in the present investigation indicate that somatostatin receptor expression might be influenced by the treatment; i.e., a higher tumor:background ratio is found in patients treated with either somatostatin analogues or IFN. Furthermore, it was found that somatostatin receptor expression correlates with the levels of U-5HIAA and p-chromogranin A in untreated patients, and that 111In-octreotide SPECT scintigraphy is more likely positive in patients with elevated U-5HIAA values. This indicates that somatostatin receptor expression and elevated U-5HIAA are more likely present in patients with highly differentiated tumors and, thus, could be of prognostic value.
 ...
PMID:Somatostatin receptor scintigraphy in patients with carcinoid tumors: comparison between radioligand uptake and tumor markers. 749 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>