Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.
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PMID:Endocrine cells producing regulatory peptides. 329 70

The antitumor action of the 2-chloroethylnitrosocarbamoyl derivatives of peptides related to the 9-13 amino acid residues of alpha-MSH/ACTH and of the C-terminal tetrapeptide analogue of gastrin have been investigated. Series of 2-chloroethylnitrosoureas attached to amino acids, di-, tri-, tetra-, or pentapeptides were examined in a primary screening system. Among these compounds the Pro-Val-, Lys-Pro-Val-, and Trp-Gly-Lys-Pro-Val-containing 2-chloroethylnitrosocarbamoyl groups were the most effective in the L1210 system. The human melanoma xenograft line was also affected by these agents, while colorectal xenografts were insensitive. A combination of tripeptide-2-chloroethyl-nitrosourea with BCNU induced more than additive growth inhibition of L1210 leukemia.
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PMID:Antitumor action of N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of biologically active polypeptide hormone fragments. 394 98

The conformation of some polypeptides and proteins in sodium dodecyl sulfate (NaDodSO4) solutions was studied by circular dichroism. The type and extent of induced structure depend on their helix- and beta-forming potential. Anionic side groups in segments of helix or beta form tend to destabilize the ordered structure unless they are protonated. beta-Endorphin has one Glu inside a predicted helical segment; its helicity in a NaDodSO4 solution is enhanced at pH below 4. alpha-Melanocyte-stimulating hormone having a Glu in a beta segment undergoes a pH-induced coil to beta transition in 1.25 mM NaDodSO4 (excess surfactant will disrupt the beta form). Reduced somatostatin assumes a beta form in 2 mM NaDodSO4 and a partial helix in 25 mM NaDodSO4, both of which are unchanged in acidic pH because it lacks -COOH groups. The unordered gastrin with five consecutive Glu's becomes helical in a NaDodSO4 solution at pH 4. Neurotensin with one Glu has no structure-forming potential and is unordered in both neutral and acidic NaDodSO4 solutions. This charge effect also manifests in segments of ordered structure for polypeptides and proteins such as glucagon, cytochrome c, parvalbumin, ribonuclease A, and lysozyme. The effect is especially predominant in tropomyosin that is rich in clusters of anionic side groups. Its more than 90% helicity is reduced to about one-half in a neutral NaDodSO4 solution, but most of it can be restored by lowering the pH to 2.4.
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PMID:Ordered conformation of polypeptides and proteins in acidic dodecyl sulfate solution. 611 37

Adrenocorticotropin (ACTH)-like and alpha-melanotropin (alpha-MSH)-like peptides have been localized to a subpopulation of cytoplasmic (secretory) granules of human antropyloric gastric cells and of fetal and neoplastic gastrin cells. These granules also store gastrin and belong to the electron-dense variety of gastrin cell granules. Gastrin cells also contain granules of low to medium electron density; these store only gastrin and do not react with ACTH or alpha-MSH antisera. The alpha-MSH immunoreactive peptide was shown also to display alpha-MSH bioactivity by a combined immunosorbent-bioassay technique. This peptide cochromatographs with synthetic alpha-MSH in several systems and is not detected in oxyntic mucosa or in gastric muscle wall. As in the pituitary intermediate lobe, the alpha-MSH-like peptide may be formed by cleavage of ACTH-like peptides also in gastrin cells. These data provide additional evidence for local formation of ACTH/alpha-MSH-related peptides in gastrin cells and suggest a heterogenous peptide make-up of endocrine cell granules.
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PMID:Adrenocorticotropin-like and alpha-melanotropin-like peptides in a subpopulation of human gastrin cell granules: bioassay, immunoassay, and immunocytochemical evidence. 626 28

Highly purified porcine neurophysin-II, prepared from pig posterior pituitary lobe tissue was injected into fifteen rabbits in the preparation of anti-neurophysin sera. All antisera, when used in association with immunohistochemical procedures, gave an immunoreaction in structures of the rat hypothalamo-neurohypophysial system. Four antisera, however, also stained cells of the arcuate nucleus, corticotrophs and melanotrophs. Staining of the latter two cell groups also occurred in tissues obtained from Brattleboro rats. Preadsorption of the latter neurophysin antisera with either alpha-MSH, beta-LPH, beta-endorphin, ACTH (1-24), ACTH (17-39), ACTH (1-39), gastrin and CCK, failed to inhibit the staining of the corticotrophs, melanotrophs and cells of the arcuate nucleus. Inhibition of staining was achieved only by preadsorption of the antineurophysin sera with the neurophysin antigen or an homogenate prepared from the anterior pituitary. These results support the observation by others that the biosynthesis of the ACTH-beta-endorphin system in the pituitary and hypothalamus may also be accompanied by the appearance of neurophysin.
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PMID:Presence of neurophysin-like material in the pituitary corticotrophs and melanotrophs and cells of the arcuate nucleus of the rat as revealed by immunocytochemistry. 632 40

Using immunoperoxidase techniques, the possible localization of pituitary regulatory peptides in fundic, antral and duodenal mucosae was investigated in both rat and man. All results obtained were similar in the two species. No glycopeptide (FSH, LH, TSH) was detected in the digestive tract. With different antisera directed against beta-lipotropin, alpha-MSH, beta-MSH, endorphins, ACTH 1-24, ACTH 17-39, a positive reaction was only obtained in the antral mucosae with an antiserum specific for the synthetic fragment 17-39 of ACTH. However neither the common precursor, proopiomelanocortin, nor the complete sequence of ACTH seem to be present in endocrine cells of the digestive tract. On the other hand, three antisera, directed against human growth hormone (GH), visualized numerous endocrine cells scattered in the glandular epithelium of the fundic and antral mucosae. Most cells were identified as ECL type in the gastric mucosae. Others are probably of the gastrin cell type in the antral mucosa, since these cells could be visualized on adjacent sections either with the antiserum against GH, or with a specific antiserum for gastrin.
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PMID:[Cytologic demonstration of immunoreactivity characteristic of adenopituitary peptides in the digestive epithelium of the rat and man]. 632 84

Sixteen peptides were injected intracerebroventricularly to test their effects on rectal temperature of rabbits in a thermoneutral environment. In initial tests 5 micrograms alpha-MSH, ACTH(1--24), oxytocin, vasopressin and glucagon altered body temperature while ACTH(1--10), cholecystokinin, contraceptive tetrapeptide, gastrin, insulin, interferon, leupeptin, LHRH, panhibin (somatostatin), and proctolin did not. Bombesin also altered body temperature but in no consistent direction. In further tests on the effective peptides 1.25--5.0 micrograms alpha-MSH and ACTH(1--24) produced dose-related decreases in rectal temperature as great as 1.0 degrees C. The same doses of oxytocin and glucagon produced small, prolonged hyperthermias which did not exceed 0.4 degrees C. Vasopressin caused rapid development of small increases in rectal temperature; temperature returned to normal in 2--3 hr. The results suggest that five of the peptides tested may have roles in central mediation of normal body temperature, hypothermia, hyperthermia and fever.
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PMID:Central administration of peptides alters thermoregulation in the rabbit. 724 7

Neuropeptides/hormones have been shown to regulate the various functions of many immunocompetent cells. A number of neuropeptides/hormones has been demonstrated to be present in the skin and a close anatomical association between calcitonin gene-related peptide (CGRP)-containing nerves and Langerhans cells (LC) has been reported. In addition to the CGRP receptor, receptors for several neuropeptides including pituitary adenylate cyclase activating polypeptide (PACAP) and gastrin releasing peptide (GRP) are found on LC, suggesting these neuropeptides might have some effects on LC. CGRP inhibits alloantigen presentation and stimulation of a specific-antigen responsive T-cell clone by LC. Pre-treatment of LC with CGRP also inhibits the elicitation of delayed type hypersensitivity (DTH) in tumor immune mice. Upregulation of B7-2 expression on LC is suppressed by CGRP, which might be, in part, responsible for the inhibitory effect of CGRP in the functional assay. The production of some inflammatory cytokines such as IL-10 by LC-like cell line XS52 is regulated by CGRP and the functional effect of CGRP appears to be at least partially mediated through the autocrine regulation of IL-10. Alpha-MSH is another neuropeptide, the effect of which has been well studied in the cutaneous immune system. Pre-treatment of mice with alpha-MSH produces inhibitory effects in contact hypersensitivity (CHS). IL-10 has been suggested to be involved in the inhibitory effect of alpha-MSH. The receptors and the functional effects of other proopiomelanocortin (POMC)-derived peptides including beta-endorphin and catecholamines on LC are under investigation.
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PMID:The effect of neuropeptides/hormones on Langerhans cells. 1034 45

Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which contain chelators for the radioisotopes 111In, 86Y, 90Y, 67Ga, 68Ga and 64Cu or for 99mTc and 188Re. and were labelled with the halogens 123I and 18F. Radiolabeled analogs of &alpha-melanocyte-stimulating hormone (&alpha-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP) and gastrin/cholecystokinin (CCK) are also being developed, evaluated in vitro and in vivo and tested for clinical application. This review focuses on the expression in tumors and the regulation of receptors for these neuropeptides as well as the development of novel chelator-peptide conjugates suitable for in vivo scintigraphy or internal radiotherapy. The state of the art of radiopeptide pharmaceuticals is illustrated with four SRIF analogs, modified with the macrocyclic chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA): [D-Phe1]-octreotide (DOTAOC), [D-Phe1, Tyr3]-octreotide (DOTATOC), vapreotide (DOTAVAP) and lanreotide (DOTALAN). DOTA is almost a universal chelator capable of strongly encapsulating hard metals such as 111In and 67Ga for Single Photon Emission Tomography (SPET), 68Ga, 86Y and 64Cu for Positron Emission Tomography (PET) as well as 90Y for receptor-mediated radionuclide therapy and radiolanthanides which exhibit different interesting decay schemes. From biodistribution studies in experimental animals and from clinical data it is concluded that DOTATOC is currently the most suitable SRIF radiopeptide with the best potential in the clinic.
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PMID:Receptor targeting for tumor localisation and therapy with radiopeptides. 1091 Oct 25