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 membrane metalloenzyme endopeptidase-24.11 has been localized by immunocytochemistry in the porcine hippocampus in the stratum oriens and stratum radiatum. Endopeptidase-24.11 was found to be approximately 10-fold more abundant in a striatal than a hippocampal membrane preparation. Both somatostatin-28 and somatostatin-14 were metabolized by endopeptidase-24.11, but the kinetics of hydrolysis markedly favoured the smaller form of the neuropeptide. After phase separation with Triton X-114 of striatal and hippocampal membrane preparations, and by using selective inhibitors, the major (> 80%) somatostatin-metabolizing activity was found to partition into the detergent-rich phase and was attributable predominantly to endopeptidase-24.11. The residual activity observed in the presence of the selective endopeptidase-24.11 inhibitor phosphoramidon was blocked by Pro-Ile or N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, inhibitors of endopeptidase-24.16 and endopeptidase-24.15, respectively. However, Pro-Ile, at comparable concentrations, was shown to inhibit endopeptidase-24.11, challenging the validity of its use as a selective inhibitor of endopeptidase-24.16. The immunocytochemical and Triton X-114 phase-separation data implicate endopeptidase-24.11, rather than endopeptidase-24.16 or endopeptidase-24.15, as the major physiological somatostatin-degrading neuropeptidase in the striatum and hippocampus.
 ...
PMID:Endopeptidase-24.11 is the integral membrane peptidase initiating degradation of somatostatin in the hippocampus. 789 Nov 11

Several neuropeptides, including neurotensin, somatostatin, bradykinin, angiotensin II, substance P, and luteinizing hormone-releasing hormone but not vasopressin and oxytocin, were actively metabolized through proteolytic degradation by cultivated astrocytes obtained from rat cerebral cortex. Because phenanthroline was an effective degradation inhibitor, metalloproteases were responsible for neuropeptide fragmentation. Neurotensin was cleaved by astrocytes at the Pro10-Tyr11 and Arg8-Arg9 bonds, whereas somatostatin was cleaved at the Phe6-Phe7 and Thr10-Phe11 bonds. These cleavage sites have been found previously with endopeptidases 24.16 and 24.15 purified from rat brain. Addition of specific inhibitors of these proteases, the dipeptide Pro-Ile and N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-4-aminobenzoate, significantly reduced the generation of the above neuropeptide fragments by astrocytes. The presence of endopeptidases 24.16 and 24.15 in homogenates of astrocytes could also be demonstrated by chromatographic separations of supernatant solubilized cell preparations. Proteolytic activity for neurotensin eluted after both gel and hydroxyapatite chromatography at the same positions as found for purified endopeptidase 24.16 or 24.15. In incubation experiments or in chromatographic separations no phosphoramidon-sensitive endopeptidase 24.11 (enkephalinase) or captopril-sensitive peptidyl dipeptidase A (angiotensin-converting enzyme) could be detected in cultivated astrocytes. Because astrocytes embrace the neuronal synapses where neuropeptides are released, we presume that the endopeptidases 24.16 and 24.15 on astrocytes are strategically located to contribute significantly to the inactivation of neurotensin, somatostatin, and other neuropeptides in the brain.
 ...
PMID:Endopeptidases 24.16 and 24.15 are responsible for the degradation of somatostatin, neurotensin, and other neuropeptides by cultivated rat cortical astrocytes. 790 52

The innervation of the sphincter of Oddi (SO) has been extensively studied experimentally, but human studies have not been published, which is why this study was undertaken. Biopsies, taken by gastroscopy-biopsy forceps from duodenal epithelium of the papilla of Vater and from ampullary epithelium after sphincterotomy, did not demonstrate nerves and could not be used for studying SO innervation. Therefore SO specimens were obtained from brain-dead organ donors (N = 5) and from autopsies (N = 14). By staining with a myelin marker S-100, a rich network of nerves was demonstrated in SO. The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI) (or its immunologically similar human equivalent peptide histidine methioninamide, PHM), neuropeptide Y, calcitonin gene-related peptide (CGRP), galanin, substance P, enkephalin, bombesin, and somatostatin were studied by immunohistochemical technique. SO demonstrated immunoreactivity for VIP, PHI (PHM), neuropeptide Y, CGRP, galanin, somatostatin, substance P, and enkephalin, but no immunoreactivity was observed for bombesin. The SO immunoreactivity was similar in specimens from organ donors and from autopsies of victims of violence without pancreatobiliary diseases (N = 3) when the specimens were taken within 48 hr of death. Autopsy specimens of SO from subjects with gallstone disease (N = 5), recurrent pancreatitis (N = 3) or periampullary carcinoma (N = 3) also demonstrated similar immunoreactivity. We conclude that VIP-, PHI- (PHM-), neuropeptide Y-, CGRP-, galanin-, substance P-, somatostatin-, and enkephalin-like immunoreactivity occur in human SO. These neuropeptides may have role in the neural control of human SO function.
 ...
PMID:Peptidergic innervation of human sphincter of Oddi. 831 11

To better understand the complex structure and function of the sphincter of Oddi (SO), the occurrence and localization of nine neuropeptides, including vasoactive intestinal polypeptide (VIP), bombesin, neuropeptide Y, peptide histidine-isoleucine (PHI), calcitonin gene-related peptide (CGRP), galanin, substance P, serotonin, and somatostatin, were studied by immunohistochemical methods in the pig SO. The SO innervation was compared to gallbladder, common bile duct, and duodenal innervation. Specimens from the SO, gallbladder, common bile duct, and duodenum demonstrated a rich network of nerves, as suggested by light microscopy and confirmed by a myelin marker S-100. SO demonstrated very strong immunoreactivity for VIP, strong immunoreactivity for neuropeptide Y and galanin, moderate immunoreactivity for PHI and CGRP, and borderline immunoreactivity for bombesin and substance P. Serotonin and somatostatin immunoreactivity was also observed, not in the nerves, but in some of the epithelial cells. The gallbladder innervation was virtually identical to the SO innervation, whereas common bile duct and duodenal innervation were slightly different. To our knowledge this is the first time that galanin- and PHI-like immunoreactivities have been observed in the SO. Our observations suggest that these peptides, along with VIP, neuropeptide Y, and CGRP, might play a role in the neural control of biliary motility.
 ...
PMID:Neuropeptides in pig sphincter of Oddi, bile duct, gallbladder, and duodenum. 846 69

The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI), calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), galanin (GAL) and enkephalins (ENK) is studied in the human celiac/superior mesenteric ganglionic complex of pre- and full-term newborns, and adult subjects by means of immunohistochemistry. The antisera used labelled nerve fibres and terminal-like networks for each examined peptide, as well as VIP- and SOM-positive postganglionic neurons. Differences in the relative amount and density of the structures immunoreactive to the various peptides were observed. Moreover, variations in the amount and type of labelled elements were appreciable for each peptide when specimens from subjects at perinatal and adult ages were compared. Double-labelling immunofluorescence for SP and each other peptide showed that co-localization with SP is very frequent for CGRP, moderate to scarce for GAL and SOM, and rare to absent for PHI, VIP and ENK. VIP-, ENK- and CGRP-immunolabeled perikarya bearing the morphological features of the small intensely fluorescent (SIF) cells occurred in the organ. The presence of a paraganglion in one of the specimens examined allowed the detection of VIP- and ENK-positive cell bodies and VIP-, ENK-, SP- and GAL-like immunoreactive varicose nerve fibres in it. The results obtained provide substantial morphological data in support of the involvement of the examined peptides in the chemical interneuronal signalling in the human celiac/superior mesenteric ganglia.
 ...
PMID:Neuropeptides in the human celiac/superior mesenteric ganglionic complex: an immunohistochemical study. 847 42

The effects of hypothalamic peptides [vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), growth hormone (GH)-releasing hormone (GHRH) and somatostatin (SRIF) on GH release from cultured bovine adenohypophysial cells were studied. The cells were incubated for 2 h with the peptides after preincubation for 3.5 days. At doses from 10(-9) to 10(-7)M VIP, the amount of GH released was significantly greater than in the controls (P < 0.05 to P < 0.001). PHI (10(-10 to 10(-7)M did not alter the bovine GH concentration in the media. Incubation with the media containing 10(-7)M GHRH, 10(-7)M VIP, and combined treatment with the VIP plus GHRH increased GH by 186, 40 and 182%, respectively (P < 0.001). Furthermore, although VIP-induced GH release was significantly decreased by SRIF compared with the treatment with VIP alone (P<0.001), the VIP significantly blunted the inhibitory effect of the SRIF on GH release by 24% when compared with that of the SRIF plus GHRH without the VIP (P < 0.05). GH release in combined treatments with VIP, GHRH and SRIF was significantly less than that of the VIP plus GHRH (P < 0.001), but it was significant 29% increase compared with the SRIF plus GHRH (P < 0.05). The combined effects of the VIP (10(-7)M) with GHRH (10(-7), 10(-8) and 10(-10)M significantly induced GH release compared with the controls (P < 0.001), but no additive effect was not observed when compared with the GHRH alone. The results indicate that VIP, but not PHI, acts directly on cultured adenohypophysial cells to induce GH release in cattle.
 ...
PMID:The interactive effects of VIP, PHI, GHRH, and SRIF on the release of growth hormone from cultured adenohypophysial cells in cattle. 857 98

The presence of distribution of several neurochemical markers in human fungiform papillae and taste buds were investigated by the immunohistochemical technique. The gustatory cells of the taste buds are in synaptic contact with sensory nerve endings, and considering the taste buds strictly as specialized sensory organs, the amounts and distribution of some of the neurochemical markers were different to what we expected. For example, few structures showed immunoreactivity to the tachykinins substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A (NKA) also for the peptides vasoactive intestinal polypeptide (VIP), neuropeptide tyrosine (NPY) and galanin, low amounts of immunoreactivity occurred. On the other hand, using antibodies to protein gene product 9.5 (PGP 9.5), protein S-100, and glutamate, numerous nerve fibres and/or immunoreactive cells were found in the fungiform papillae, in the epithelium, in the connective tissue and around blood vessels, as well as in or near taste buds. Incubation with the antibodies against somatostatin, enkephalin, bombesin, peptide histidine isoleucine amide (PHI), cholecystokinin (CCK)/gastrin and dopamine-beta-hydroxylase (DBH) was negative for the fungiform papillae. In conclusion, the present study has shown several immunoreactive structures using antibodies against certain neurochemical markers. Further investigations will hopefully correlate these morphological findings with functional taste perception data. Future studies of patients with taste disorders or other pathological changes correlated with taste and tongue will also be of utmost importance.
 ...
PMID:Neurochemical markers of human fungiform papillae and taste buds. 857 44

Merkel cells (MCs) are specialized sensory cells widely distributed in the epithelia of vertebrates. A variable immunohistochemical pattern of neuronal and neurotransmitter markers has been demonstrated in MCs of several species including man. In the present study, we investigated the expression of neurochemical markers in a selected population of human cutaneous MCs by immunofluorescence. The structural neural proteins protein gene product 9.5 and neuron-specific enolase were found to be the most reliable markers for MC identification. Moreover, neurofilament immunoreactivity was shown in a small subset of epidermal MCs. Among the neurotransmitter markers, evidence for expression of calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine isoleucine amide, neuropeptide Y, neurokinin A, galanin, substance P, somatostatin and phenylethanolamine N-methyltransferase was found. These immunoreactivities were highly variable as far as number of positive cells and staining intensity were concerned. The results indicate that a complex and heterogeneous immunophenotype can be expressed even within a homogeneous population of human MCs.
 ...
PMID:Neurochemical markers in human cutaneous Merkel cells. An immunohistochemical investigation. 860 44

The mammalian pineal gland contains multiple afferent peptidergic nerve fibres. Sympathetic nerve fibres, with their origin in the superior cervical ganglia, contain neuropeptide Y colocalized with norepinephrine. Other pinealopetal nerve fibres, probably originating in the pterygopalatine ganglion, contain vasoactive intestinal peptide and peptide histidine isoleucine. Fibres containing substance P and calcitonin gene-related peptide have also been demonstrated in pinealopetal nerve fibres. These fibres might originate in the trigeminal ganglion. The neurotransmitter content of the fibres of the central innervation, innervating the gland from the brain via the pineal stalk, has not been elucidated. However, strong indications for the presence of neuropeptide Y, substance P, somatostatin, and vasopressin in these fibres have been presented. Recent immunohistochemical studies have further shown the presence of subtypes of pinealocytes containing neuropeptides. Thus, pinealocytes containing beta-endorphin, leu-enkephalin, and somatostatin have been demonstrated in the gland. Immunohistochemistry at the electron microscopical level has shown, that in some species, leu-enkephalin containing pinealocytes make synaptic contacts with other pinealocytes indicating of paracrine regulation of the pineal gland. It must however be emphasized that large interspecies variations exist with regard to the peptidergic pineal innervation and its content of peptidergic cells.
 ...
PMID:The chemical neuroanatomy of the mammalian pineal gland: neuropeptides. 874 61

Several studies have shown that exogenous human growth hormone (HGH) exerts an anabolic effect on protein metabolism in surgical patients with mild or moderate catabolism. However, contradictory results have been demonstrated in polytrauma patients where HGH did not improve protein metabolism. Aim of this study was to evaluate whether the pharmacokinetics of recombinant biosynthetic human GH (r-HGH) are altered in critically ill patients. After an overnight fast, r-HGH was infused at a rate of 460 micrograms/h/kg/bw during 120 min to five intensive care unit (ICU) patients. The patients were catabolic (nitrogen balance -11 +/- 0.5), showed normal liver function, and only one patient had a slightly impaired kidney function (creatinine > 1.5 mg/dl). Endogenous GH secretion was suppressed by continuous infusion of 50 micrograms/m2/h somatostatin. From plasma GH curves, elimination half life (t1/2kle), whole body clearance (Cltot) and steady state distribution space (DS) were calculated in an open two compartment model. Additionally, the effects of r-HGH infusion on plasma insulin, glucagon and amino acid concentrations were evaluated. T1/2kle was 19.6 +/- 2.3 min, Cltot 2.9 +/- 0.4 ml/kg/bw/min and DS 76.4 +/- 3.8 ml/kg/bw for 90 min. The plasma levels of total amino acids including the branched chain amino acids valine, leucine and isoleucine and of glutamine were significantly higher during r-HGH infusion than during the basal and somatostatin periods. In conclusion, the elimination of r-HGH in catabolic ICU patients is not different from that of healthy volunteers.
 ...
PMID:Human growth hormone kinetics in critically ill patients. 876 7


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