Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Using an immunocytochemical procedure a wide range of immunoreactive vertebrate bioactive peptides (BAPs) has been found in hemocytes of Viviparus ater: bombesin, calcitonin, CCK-8, CCK-39, GH, glucagon, insulin, oxytocin, neurotensin, secretin, serotonin, somatostatin, substance P, vasopressin, and VIP. 2. No immunostaining was observed for antigastrin and antithyroglobulin antibodies. 3. The presence of BAP-like molecules in hemocytes suggests a correlation between hemocyte and APUD cells and is evidence of a relationship between the neuroendocrine and the immune systems.
Cell Mol Neurobiol 1992 Oct
PMID:The presence of immunoreactive vertebrate bioactive peptide substances in hemocytes of the freshwater snail Viviparus ater (Gastropoda, Prosobranchia). 136 24

Using the polymerase chain reaction technique with degenerative primers, we obtained from a rat pituitary cDNA library a cDNA fragment, rAP236, that exhibited considerable homology to known receptors that belong to the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. Oligonucleotides to this fragment were used as probes to obtain a full-length cDNA from the rat pituitary cDNA library. This clone, rAP6-26, encoded a 383-amino acid protein with seven putative transmembrane domains that are characteristic of G protein-coupled receptors. The predicted amino acid sequence of the rAP6-26 cDNA exhibits 56-66% homology to recently cloned somatostatin (SRIF) receptors. Membranes prepared from COS-7 cells transfected with the rAP6-26 cDNA showed specific binding of 125I-Tyr11-SRIF, thus identifying the cDNA clone as a novel SRIF receptor. Radioligand binding competition analysis using somatostatin-28 (SRIF-28) and a number of cyclic SRIF analogs revealed that SRIF-28 was the most potent competitor of 125I-Tyr11-SRIF binding, with a approximately 30-fold greater affinity for the receptor than that of SRIF. In addition, binding of 125I-Tyr11-SRIF was markedly reduced in the presence of Na+ ions and GTP, indicating coupling of rAP6-26 receptors to inhibitory G proteins in COS-7 membranes. In adenylyl cyclase assays, forskolin-induced cAMP accumulation was inhibited by SRIF and SRIF-28, thus confirming that the rAP6-26 cDNA encodes a functional receptor protein. By Northern blot analysis, a approximately 2.6 kilobase mRNA encoding the receptor was present in the pituitary but not in the liver, small intestine, kidney, pancreas, cerebellum, or cortex. Lack of receptor mRNA expression in the brain was confirmed by in situ hybridization histochemical studies. Thus, we report the cloning of a novel rat pituitary SRIF receptor, termed SSTR4, that has marked preferential affinity for SRIF-28 and is linked to inhibition of adenylyl cyclase.
Mol Pharmacol 1992 Dec
PMID:Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28. 826 65

The somatostatin concentrations of cerebrospinal fluid (CSF) and brain tissue in 16 refractory epileptic patients were measured simultaneously by a radioimmunoassay (RIA) method. An increased level of somatostatin was found in the epileptic foci of cerebral cortex, determined by the cortical EEG. There were significant differences among the epileptic foci (75.58 +/- 6.58 pg/mg wet wt, +/- SEM), nonfocal tissues (37.04 +/- 6.55 pg/mg), and normal tissues of control patients (47.69 +/- 10.12 pg/mg), p < 0.001 and p < 0.05, respectively. The somatostatin concentrations of CSF in 11 epileptic patients were determined before (257.78 +/- 19.11 pg/mL) and after (178.36 +/- 8.78 pg/mL) the removal of epileptic focal area, and a dramatic decrease of the CSF somatostatin concentration after operation was detected (p < 0.01). We also found that the somatostatin level of cerebral scar induced by head injury in cases of posttraumatic epilepsy was highest (106.39 +/- 12.41 pg/mg). The results suggested that the surgical removal of the epileptic focal area in refractory epileptic patients may reduce the increased central somatostatin level, which could play an important part in the pathophysiological process of refractory epilepsy.
Mol Chem Neuropathol 1992 Dec
PMID:Somatostatin concentrations in cerebrospinal fluid and brain tissue of patients with refractory epilepsy. 136 76

The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, hyperinsulinemia and other endocrine abnormalities. In order to elucidate pathogenetic mechanisms contributing to disturbed feeding behavior in these animals, the effect of food restriction on three hypothalamic neuropeptides involved in the control of food intake was studied. Eighteen male obese and 18 lean Zucker rats were randomly divided into two groups: half of the animals were food-restricted for 2 weeks, while the other half served as controls and were fed ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were determined using in situ hybridization technique. In addition, plasma insulin and corticosterone concentrations were analyzed. Food restriction significantly increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker phenotypes, while the expressions of preproCRF mRNA in the paraventricular nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not altered. The expression of preproNPY mRNA was significantly greater in control obese animals compared to control lean animals. Food restriction lowered plasma insulin levels, but did not change plasma corticosterone levels. It is concluded that food restriction specifically activates NPY gene transcription in the arcuate nucleus the response being similar in both Zucker phenotypes. The results suggest that orexigenic NPY plays a role in the adaptation to altered feeding status.
Brain Res Mol Brain Res 1992 Dec
PMID:Hypothalamic neuropeptide expression after food restriction in Zucker rats: evidence of persistent neuropeptide Y gene activation. 136 27

Indirect evidence links sensory nerves with mast cells (MC) in inflammatory reactions of airway, skin, and intestine. Isolated MC secrete histamine, serotonin, and other inflammatory mediators in response to neuropeptides such as substance P (SP) in vitro. To obtain direct evidence of nerve/MC interactions, we used a tissue culture model involving the co-culture of murine sympathetic neurons and rat basophilic leukemia (RBL) cells (homologous to mucosal MC). An electrophysiologic analysis of the consequences of neuron/RBL cell contacts showed that neurite contact with RBL cells reduced the control input resistance (Ro) of 61.8 +/- 3.2 (n = 110) M omega to 22.4 +/- 4.8 (n = 13) M omega (P less than 0.01) without change in the membrane potential. Time course studies showed that Ro of RBL cells with neurite contact was always lower by 30 to 54% than adjacent RBL cells lacking such contact. This effect was not seen in RBL cells cultured on rat fibroblasts. Direct application of SP, bradykinin, and somatostatin, but not acetylcholine, noradrenaline, or the putative neurotransmitter ATP, could partly mimic the effect of neurite contact. Therefore, neurotransmitter release from sympathetic neurons in contact with RBL cells may decrease RBL cell membrane resistance, possibly leading to activation.
Am J Respir Cell Mol Biol 1992 May
PMID:Sympathetic nerve contact alters membrane resistance of cells of the RBL-2H3 mucosal mast cell line. 137 18

To investigate the interaction of guanine nucleotide-binding regulatory proteins (G proteins) with the agonist-bound brain somatostatin (SRIF) receptor, rat brain SRIF receptor/G protein complexes were solubilized and immunoprecipitated with peptide-directed antisera selective for the different subtypes of G protein alpha subunits (G alpha). In the absence of agonist, solubilized SRIF receptor/G proteins complexes could be immunoprecipitated by antiserum 8730, which is directed against the carboxyl-terminal region of Gi alpha and recognizes all Gi alpha subtypes, and by antiserum 3646, which selectively interacts with internal regions of Gi alpha 1. In contrast, antiserum 1521, which is directed against an internal region of Gi alpha 2, and antiserum 9072, which is directed against the carboxyl-terminal region of Go alpha, did not immunoprecipitate the SRIF receptor. After the binding of agonist to solubilized SRIF receptors, antisera 9072 and 1521, as well as antisera 8730 and 3646, were able to immunoprecipitate the agonist-bound SRIF receptor/G protein complexes, indicating that agonist interaction with SRIF receptors maintained receptor association with Gi alpha 1 and promoted receptor association with Go alpha and, to a lesser extent, Gi alpha 2. Antiserum 1518, which is directed against Gi alpha 3, uncoupled SRIF receptors from Gi alpha and did not immunoprecipitate the agonist-bound or agonist-free brain SRIF receptor. These findings indicate that differences exist in the interaction of the agonist-free and agonist-bound SRIF receptors with G proteins. The binding of agonists to SRIF receptors promotes the association of the receptor with Go alpha and, to a lesser extent, Gi alpha 2, indicating that these G proteins, along with Gi alpha 1 and Gi alpha 3, may be involved in coupling SRIF receptors to cellular effector systems.
Mol Pharmacol 1992 Sep
PMID:Agonist binding to rat brain somatostatin receptors alters the interaction of the receptors with guanine nucleotide-binding regulatory proteins. 140 98

The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone in immature cells, expression of neuronal markers during islet cell development, and the pluripotentiality of clones of insulinoma cells to develop into cells expressing other islet cell hormones. The four mature endocrine cell types assume a particular organization within the islets of Langerhans in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage. In contrast, insulinoma cells are more islet-like in their phenotype and show less neuronal traits.
Mol Endocrinol 1992 Aug
PMID:Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. 140 10

In this report, we describe the isolation and initial characterization of a Drosophila protein, dCREB-A, that can bind the somatostatin cyclic AMP (cAMP)-responsive element and is capable of activating transcription in cell culture. Sequence analysis demonstrates that this protein is a member of the leucine zipper family of transcription factors. dCREB-A is unusual in that it contains six hydrophobic residue iterations in the zipper domain rather than the four or five commonly found in this group of proteins. The DNA-binding domain is more closely related to mammalian CREB than to the AP-1 factors in both sequence homology and specificity of cAMP-responsive element binding. In embryos, dCREB-A is expressed in the developing salivary gland. A more complex pattern of expression is detected in the adult; transcripts are found in the brain and optic lobe cell bodies, salivary gland, and midgut epithelial cells of the cardia. In females, dCREB-A is expressed in the ovarian columnar follicle cells, and in males, dCREB-A RNA is seen in the seminal vesicle, ejaculatory duct, and ejaculatory bulb. These results suggest that the dCREB-A transcription factor may be involved in fertility and neurological functions.
Mol Cell Biol 1992 Sep
PMID:A cyclic AMP-responsive element-binding transcriptional activator in Drosophila melanogaster, dCREB-A, is a member of the leucine zipper family. 150 8

Cyclic AMP regulates a variety of cellular responses through activation of the catalytic subunit of cAMP-dependent protein kinase. The cDNAs for two protein isoforms of the catalytic subunit, C alpha and C beta, were placed into expression vectors, and their ability to stimulate cAMP-dependent transcription of the human enkephalin promoter was examined in transiently transfected CV-1 cells. Expression vectors for C alpha and C beta that were directed by the human cytomegalovirus promoter produced up to 350- and 200-fold increases in chloramphenicol acetyltransferase activity, respectively, when cotransfected with the ENKAT-12 reporter plasmid. Transcriptional activation was shown to be dependent upon functional kinase activity by point mutations in catalytic subunit vectors which eliminated activation. Transcriptional activation by C alpha and C beta was eliminated when the cAMP response elements (CREs) were deleted from the native enkephalin promoter, but activation was recovered when this region was replaced with an oligonucleotide containing two copies of the somatostatin CRE consensus TGACGTCA. C alpha expression vectors were found to produce 2-fold greater transcriptional activation than C beta expression vectors. These results were most likely due to the cellular kinase activity produced by the catalytic subunit expression vectors and did not appear to be dependent on CRE motif or substrate specificity. In vitro mutagenesis indicates that neither C alpha nor C beta requires N-terminal myristylation for transcriptional activation, but threonine-197 is critical to subunit function.
Mol Endocrinol 1991 Jul
PMID:Regulation of the human enkephalin promoter by two isoforms of the catalytic subunit of cyclic adenosine 3',5'-monophosphate-dependent protein kinase. 165 33

A week daily administration of cysteamine (CYS, 300 mg kg-1) lowered plasma aldosterone concentration in rats, without affecting PRA, kalaemia and the plasma levels of ACTH and corticosterone. Prolonged CYS treatment caused a notable hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells, without inducing any apparent change in zona fasciculata morphology. Isolated ZG cells from CYS-treated rats evidenced a notable enhancement in their basal and maximally-stimulated productions of aldosterone and corticosterone. All these effects of chronic CYS administration were completely reversed by the simultaneous infusion of rats with somatostatin (SRIF, 12 micrograms kg-1 h-1). CYS exposure was not found to directly affect the secretory activity of isolated ZG cells from normal rats. Since CYS is known to be a specific depletor of SRIF in different organs of rats, these findings suggest that endogenous SRIF may be involved in the modulation of ZG function.
J Steroid Biochem Mol Biol 1991 Apr
PMID:Effects of prolonged cysteamine administration on the rat adrenal cortex: evidence that endogenous somatostatin is involved in the control of the growth and steroidogenic capacity of zona glomerulosa. 167 25


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