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)

In order to investigate the possible involvement of corticotropin-releasing factor (CRF) and somatostatin (SRIF) on thyrotropin-releasing hormone (TRH) neuronal cell activity in the rat hypothalamic paraventricular nucleus, we have proceeded to the simultaneous localization of CRF or SRIF and TRH. For this purpose, we used a dual immunostaining procedure that employed antibodies to CRF and SRIF and peroxidase-labeled goat anti-rabbit IgG as a first sequence, and antibodies to a cryptic fragment (Phe178-Glu199) of pro-TRH (to label TRH neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second sequence. A rich innervation of the paraventricular nucleus by immunoreactive CRF and SRIF fibers was observed. A large number of CRF and SRIF nerve endings were seen intimate anatomic proximity and often appeared to surround TRH-containing cell bodies. These results strongly suggest that TRH neurons might be regulated by both CRF and SRIF. These interactions might be the neuroanatomical basis for the already observed inhibitory effects of CRF and SRIF on TRH release.
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PMID:Neuroanatomical connections between corticotropin-releasing factor (CRF) and somatostatin (SRIF) nerve endings and thyrotropin-releasing hormone (TRH) neurons in the paraventricular nucleus of rat hypothalamus. 135 8

In this immunocytochemical study, we have analyzed the developmental profile and phenotypic expression of the endocrine cell antigens chromogranin, 5-hydroxytryptamine, gastrin/cholecystokinin, cholecystokinin (9-20), somatostatin, somatostatin 28 (1-14), somatostatin cryptic peptide, glucagon, glucagonlike peptides 1 and 2, glicentin, peptide YY, glucose-dependent insulinotropic peptide, secretin, neurotensin, and substance P in human fetal stomach and intestine. All currently identifiable endocrine cell types were detected by 10 wk of gestation. Immunostaining for the endocrine cell marker chromogranin revealed abundant endocrine cells in the earliest specimens (8 wk of gestation) with a relatively higher frequency in both proximal duodenum and distal colon/rectum compared with other areas. Quantification of endocrine cells showed an increase with age that was roughly parallel to the growth of the gut as a whole. These studies show that the diversity of the endocrine component of the gut appears to be established by 10 wk of gestation and that gut activity is preceded by the development of a fully differentiated endocrine component, which may subserve or even initiate the onset of functional maturity.
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PMID:Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells. 272 79

The search for a peptide corresponding to the NH2-terminus of somatostatin-28 (SS-28) in tissues has led to the isolation and characterization of somatostatin-28[1-12] from pancreas and hypothalamus. Somatostatin-28[1-12]-like immunoreactivity [SS-28 [1-12]-LI] is widely distributed throughout the central nervous system and the digestive system of rodents and primates, reaching levels comparable to those of somatostatin-14 (SS-14). Antibodies directed against the C-terminal end of the dodecapeptide are more specific and constitute excellent markers for the "prosomatostatin" system in mammalian tissues. In rat brain, SS-28[1-12]-LI material is highly concentrated in nerve fibres and terminals, especially in the median eminence, layer I of neocortex, the outer molecular layer of the dentate gyrus and the striatum. Additionally, immunoreactivity is observed in large multipolar or occasionally pyramidal-like neurons of the neocortex. SS-28[1-12] is secreted from hypothalamus and amygdala by a calcium dependent mechanism. No biological role is presently known for the dodecapeptide. Two other peptides of Mr = 8000 (8 K) and Mr = 5000 (5 K) which contain SS-28[1-12] at their carboxy-termini are present in acid extracts from rat pancreas, brain and spinal cord. These two peptides were isolated from an acid extract of rat brains using ion-exchange chromatography, gel permeation chromatography and reverse-phase HPLC. Results from amino acid analysis and partial sequencing were compared to the sequence of the cDNA encoding rat pre-prosomatostatin (prepro-SS) and revealed that the 8 K peptide is a 76 amino acid molecule corresponding to prepro-SS[25-100] and that the 5K peptide, which contains 44 amino acids, corresponds to prepro-SS [57-100]. The 5 K peptide was generated after cleavage of a Leu-Leu bond at position 56-57 of prepro-SS. The four most predominant peptides of the "prosomatostatin system" presently characterized are: SS-14, SS-28[1-12], SS-28 and prepro-SS[25-100]. Studies on pooled perfusates from rat hypothalamic tissue show that prepro-SS[25-100] is released with SS-28[1-12] in vitro and accounts for 22% of the total SS-28[1-12]-like immunoreactive material released during depolarization. The 5 K peptide is apparently not secreted. The presence of prepro-SS[25-100] in brain implies that, first, prosomatostatin can serve as an immediate precursor for SS-14 without going through SS-28 as an intermediate step and second, other peptides could conceivably be derived from the cryptic portion of the precursor.
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PMID:Somatostatin-28 [1-12]-like peptides. 286 51

Antisera raised against rat somatostatin cryptic peptide (RSCP; corresponding to amino acids 63-77 of rat pro-somatostatin), somatostatin-28-(1-12) and somatostatin-28-(17-28) were used to compare the morphological distribution of these pro-somatostatin-derived sequences within the gastroenteropancreatic system of six mammalian species, including man. Using the immunogold staining procedure, RSCP, SS28-(1-12) and SS28-(17-28) immunoreactivity was found to be present in all the D cells of the tissues investigated. Extra-islet RSCP and SS28-(1-12) immunoreactive cells were also identified in some species. RSCP, SS28-(1-12) and SS-28-(17-28) immunoreactivities were also present in a single case of human duodenal somatostatinoma. Immunostaining of serial ultrathin sections from all specimens in this study revealed that RSCP and both somatostatin immunoreactivities were co-localised in a majority of the reactive cells. Corroborative evidence was obtained by double immunogold staining which further showed that RSCP, SS28-(1-12) and SS28-(17-28) immunoreactivities were co-localised to individual secretory granules in D type cells, both normal and tumour. RSCP and SS28-(17-28) immunoreactivities were invariably co-localised, whereas SS28-(1-12) immunoreactivity was restricted to a sub-population of secretory granules. Our findings suggest that RSCP immunoreactivity is conserved in a number of mammalian species and is stored in each secretory granule type. Consequently, detection of the RSCP sequence may serve as a useful marker for somatostatin-producing systems throughout the diffuse neuroendocrine system.
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PMID:Somatostatin-containing D cells exhibit immunoreactivity for rat somatostatin cryptic peptide in six mammalian species. An electron-microscopical study. 287 39

MTC is characterized by multiple humoral and hormonal manifestations. Although calcitonin is the specific marker of the disease, somatostatin, the pro-opiomelanocortin derived peptides and bombesin--among hormones produced by the tumor--can represent an exacerbation of normal C cells potentialities through genome derepression induced by the cancer. In this paper, the functional polymorphism of princeps tumoral markers and the endocrinological aspects of this neoplasia are reviewed. Molecular biology has been instrumental in discovering new tumoral peptides ("ancestral" CT forms, cryptic peptide and CGRP) and methods of CT detection; therefore, the role of CT could be better evaluated. In addition to its calciotropic role, CT acts also as a neuromodulator on some hypophyseal hormones. Conversely, CT secretion is also regulated by amines and neuropeptides, providing the basis of potential hormonal treatment.
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PMID:[Tumor markers of medullary cancer of the thyroid body. Basic and endocrine aspects]. 290 Jun 20

Using an antiserum to a 15-amino acid synthetic peptide corresponding to amino acids 63-77 of rat preprosomatostatin (rat somatostatin cryptic peptide, RSCP), we have compared the distribution of immunoreactive RSCP (IR-RSCP) with that of immunoreactive somatostatin-14 in the rat brain. IR-RSCP was present in neuronal cell bodies, processes, and axon terminals in the hypothalamic tuberoinfundibular system as well as in diverse regions of the central nervous system in an identical distribution to immunoreactive somatostatin. These observations indicate that in neurons the somatostatin prohormone or the NH2-terminal extension peptide of somatostatin-28 (or both) is stored and transported intracellularly along with somatostatin 14. In addition, the presence of IR-RSCP in nerve terminals suggests that this material may be secreted as a hormone or neuromodulator and may serve as a biologic marker of somatostatin secretion.
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PMID:Prosomatostatin-specific antigen in rat brain: localization by immunocytochemical staining with an antiserum to a synthetic sequence of preprosomatostatin. 613 83

Small peptide hormones (less than 50 amino acids) are synthesized as larger inactive precursors. Work from several laboratories, including our own, has implicated the propeptide of various precursors in mediating intracellular transport and targeting to secretory granules. We previously demonstrated that the proregion of prosomatostatin, one of the simplest peptide hormone precursors, when fused to alpha-globin, enabled the globin polypeptide to be transported to the regulated secretory pathway. To identify sorting motifs in this propeptide, we have now constructed a chimera comprising the somatostatin signal peptide and proregion fused to chloramphenicol acetyl transferase (CAT) and a control protein consisting of the signal peptide fused to CAT, both of which were expressed in rat anterior-pituitary GH3 cells. Both molecules were translocated into the endoplasmic reticulum (ER) efficiently and core-glycosylated on the single cryptic N-linked glycosylation site present in CAT. Surprisingly, the glycosylated propeptide-CAT and signal without CAT were degraded intracellularly with half-lives of 30 min and 90 min, respectively. Based on the kinetics of degradation, temperature sensitivity, and resistance to lysosomotrophic agents, we suggest that degradation occurred in the ER. Our data imply that the pro-region is not an a priori universal sorter, but only directs heterologous peptides to the secretory pathway when the passenger peptide assumes a secretion-competent conformation.
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PMID:Intracellular degradation of prohormone-chloramphenicol-acetyl-transferase chimeras in a pre-lysosomal compartment. 790 39

TRH and somatostatin (SRIH) are well known to stimulate and to inhibit TSH secretion respectively. However, the mechanisms underlying the effect of SRIH on thyrotrophs are still not understood. We have previously shown in vitro that the TSH response to TRH is potentiated in a Ca(2+)-dependent fashion through the activation of dihydropyridine (DHP)-sensitive Ca2+ channels by the prepro-TRH (160-169) cryptic peptide (PS4) and tri-iodo-L-thyronine (T3), when the hormone was added shortly before a TRH pulse in order to avoid its genomic effect. Using perifused rat pituitary fragments, the present study has shown that SRIH inhibits, in a dose-dependent manner, the TSH response to physiological concentration of TRH (10 nM) and reverses the Ca(2+)-dependent potentiation of that response induced either by PS4 or by T3. We have also demonstrated that the inhibition by SRIH of the T3 potentiation of TRH-induced TSH secretion is pertussis toxin-sensitive. Our data suggest that SRIH inhibits the PS4 and T3 potentiation of TRH-induced TSH secretion through the inactivation of DHP-sensitive Ca2+ channels. Using primary cultures of rat anterior pituitary cells and videomicroscopy, we have already demonstrated that TRH, as well as PS4 and T3, are able to increase intracellular Ca2+ concentration ([Ca2+]i) rapidly, in 15 s. Our study has shown that SRIH is able to abolish the acute rise in [Ca2+]i induced either by PS4 or by T3. Since [Ca2+]i responses to PS4 and T3 are also abolished by the DHP nifedipine, our results suggest that [Ca2+]i changes in PS4- or T3-sensitive pituitary cells depend directly or indirectly on the activation of DHP-sensitive Ca2+ channels and that the inhibitory effect of SRIH may be mediated by inactivation of this type of channel.
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PMID:Somatostatin blocks the potentiation of TRH-induced TSH secretion from perifused pituitary fragments and the change in intracellular calcium concentrations from dispersed pituitary cells elicited by prepro-TRH (PS4) or by tri-iodothyronine. 927 64

Studies aimed at analyzing the deleterious effects of excess alcohol in the brain have revealed structural alterations that are often associated with functional and behavioral disturbances. Among the neuronal damage related to prolonged alcohol exposure, alterations in the synthesizing capabilities and levels of expression of neuroactive peptides have been increasingly reported. Actually, such changes frequently represent the sole repercussion of acute and short-term exposure to ethanol. This review gathers the existing data on the effects of ethanol exposure on the synthesis and expression of hypothalamic peptides. Amid those that can act both as neurotransmitters and neurohormones, we allude to vasopressin, corticotropin-releasing hormone, thyrotropin-releasing hormone and pro-opiomelanocortin and related peptides produced by paraventricular, supraoptic and arcuate neurons. With respect to peptides that act exclusively as neurotransmitters, we address the effects of alcohol on vasoactive intestinal polypeptide, gastrin-releasing peptide, somatostatin and vasopressin synthesized by suprachiasmatic neurons. Hypothalamic neurons that produce peptides that act as neurotransmitters are supposed to be modulated primarily by influences exerted by neuronal afferents, whereas those producing peptides that additionally act as neurohormones are also regulated by peripheral stimuli (e.g., plasma levels of circulating hormones, osmotic challenges). These peculiar features endue the hypothalamus with characteristics that are particularly propitious to enlighten the still cryptic mechanisms underlying the ethanol effects on protein synthesis.
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PMID:Effects of alcohol on the synthesis and expression of hypothalamic peptides. 1021 Jan 63