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)

Plasma and cerebrospinal fluid (CSF) concentrations of three well-known satiety neuropeptides, cholecystokinin (CCK), somatostatin and calcitonin gene-related peptide (CGRP), along with two powerful orexigenic neuropeptides, neuropeptide Y (NPY) and beta-endorphin have been measured in elderly persons with idiopathic anorexia and normal weight healthy subjects in a similar age range. Plasma and CSF immunoreactivity levels of the two main fractions of CCK (CCK8s and CCK33) after being separated by HPLC were measured by a radioimmunoassay (RIA) developed in our laboratory, whereas the other neuropeptides were assayed by commercially available RIA kits. Elderly underweight anorectic patients had significantly lower levels of beta-endorphin but increased concentrations of NPY in both plasma and CSF when compared to controls. In addition to significantly higher levels of CCK8s but not CCK33 in plasma, we found a trend to higher CSF concentrations of CCK8s and a positive correlation between the body mass index and either beta-endorphin (r = 0.58, P < 0.05) or CCK8s (r = 0.69, P < 0.01) concentrations in CSF in the anorectic group. CSF somatostatin concentrations were decreased significantly, but plasma somatostatin levels and plasma and CSF concentrations of CGRP were similar in senile anorectics and controls. Treatment of five anorectic patients with megestrol acetate, 480 mg daily for 6 months, reversed only the decrease in CSF beta-endorphin levels but did not normalize the body weight or the fat body mass. On the basis of our findings, we hypothesize that a decrease in CSF beta-endorphin concentration along with a rise in plasma levels of CCK8s might be accounted for the primary anorexia of aging.
 ...
PMID:Alterations in plasma and cerebrospinal fluid levels of neuropeptides in idiopathic senile anorexia. 790 1

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.
 ...
PMID:Cholecystokinin is a physiological regulator of gastric acid secretion in man. 795 87

1. A possible interaction between cyclic AMP and nitric oxide (NO) in mediating the relaxant effect of vasoactive intestinal polypeptide (VIP) on intestinal smooth muscle cells has been investigated. The effects of the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), have been studied on VIP-, forskolin-, and 8 bromo-cyclic AMP- induced relaxation of cells, dispersed by enzymatic digestion of muscle strips from the circular layer of guinea-pig ileum. 2. VIP alone did not modify the length of isolated muscle cells. By contrast, when the cells were contracted by cholecystokinin octapeptide, CCK8 (10 nM), VIP inhibited this contraction, inducing a concentration-dependent relaxation of the cells. Maximal relaxation was induced by 1 microM VIP (EC50 = 408.2 +/- 16.7 pM). 3. N-ethylmaleimide, inhibitors of adenylate cyclase or somatostatin, abolished the relaxing effect of VIP. (R)-p-cAMPs, an antagonist of cyclic AMP on protein kinase A also inhibited the VIP-induced relaxation by 92.1 +/- 6.3%. Inhibitors of nitric oxide synthase (NOS), L-NAME and L-NMMA, partially inhibited VIP-induced relaxation. The effect of L-NAME was reversed by L-arginine but not by D-arginine. 4. (R)-p-cAMPS and L-NAME also inhibited the cell relaxation induced either by forskolin which directly stimulates adenylate cyclase activity or 8-bromo-cyclic AMP, an analogue of cyclic AMP. 5. When cells were incubated for 30 min with dexamethasone 10 microM, a glucocorticoid known to decrease the synthesis of iNOS, the relaxing effect of a maximal concentration of VIP was decreased by 52 +/- 4% and L-NMMA had no further effect on this residual VIP-induced relaxation. Milrinone, a phosphodiesterase type III inhibitor, potentiated the relaxant effect of VIP. 6. These data demonstrate that the intracellular pathway mediating the relaxant effect of VIP in intestinal smooth muscle cells includes the sequential activation of adenylate cyclase, protein kinase A, activation of NOS and finally production of NO and cyclic GMP. NO could in turn regulate the cyclic AMP-dependent pathway of cell relaxation.
 ...
PMID:VIP-induced relaxation of guinea-pig intestinal smooth muscle cells: sequential involvement of cyclic AMP and nitric oxide. 876 68

In the present study, the effects of experimental lead pollution on gut endocrine cells have been determined in the goldfish Carassius carassius (L.) var.auratus by immunocytochemical reactions. In the mucosa and submucosa, only vasoactive intestinal polypeptide- and 5-HT-like immunoreactive nerve fibers were observed. Endocrine cells displaying immunoreactivity against gastrin, CCK8, metenkephalin, bombesin, neuropeptide Y, pancreatic polypeptide, substance P, secretin, somatostatin and vasoactive intestinal polypeptide antibodies were detected. No immunoreactivity against glucagon, insulin and 5-HT antibodies was revealed in the endocrine cells. Some modifications appeared evident in the endocrine cells 48-96 h after lead intoxication, and can be summarized as follows: 1) discharge of secretory granules (secretin- and vasoactive intestinal polypeptide-like peptides), up to the extent that the cells appeared to be depleted of secretory material; 2) increase of immunoreactivity in the endocrine cells (met-enkephalin- and pancreatic polypeptide-like peptides) or in the frequency of positive cells (met-enkephalin-like peptide); 3) no variations (gastrin-, CCK8, bombesin-, somatostatin- and substance P-like peptides). The alterations were not enhanced by long term treatment. Nerve fibers did not show modifications.
 ...
PMID:Immunocytochemical study of endocrine cells in the gut of goldfish Carassius carassius (L.) var. auratus submitted to experimental lead intoxication. 911 38

The effects of bombesin (BM) on the canine gallbladder motility was studied under two different experimental conditions: (i) in conscious dogs with a balloon chronically implanted into the gallbladder lumen where intragallbladder pressure was recorded in mm Hg by means of a pressure transducer, and (ii) in smooth muscle preparations isolated from different regions of the gallbladder where the contractions were recorded isometrically by means of mechanoelectrical transducers. Similar to CCK8 bolus injection of. BM i.v. increased the gallbladder pressure in a dose-dependent manner. The response was characterized by a slow increase of the tone and a gradual restoration (in 4 to 8 min) of the background activity. The threshold dose and the maximum dose were 30 ng/kg and 100 ng/kg for BM and 1 ng/kg and 10 ng/kg for CCK8, respectively. Both atropin (10 to 50 micrograms/kg) and hexamethonium (0.5 to 3 mg/kg) injected i.v. 5 to 10 min before BM strongly reduced or even abolished the gallbladder response to BM. Somatostatin (1 to 2 micrograms/kg) and VIP (0.5 to 1 microgram/kg) injected 3 to 5 min before BM also exerted a strong inhibitory effect on the canine gallbladder response to BM. However BM (up to 10(-6) M) had no effect on the spontaneous or electrically-induced contractions of the canine gallbladder smooth muscle preparations. The results suggest the involvement of prejunctional cholinergic-, somatostatinergic- and VIP-ergic pathways in the bombesin-induced increase of the gallbladder pressure of conscious dogs.
 ...
PMID:Effects of bombesin on the canine gallbladder motility: in vivo and in vitro experiments. 1034 19

Endocrine cells containing gastrin/cholecystokinin (CCK)-like immunoreactivity were localized to the islet tissue in the pancreas of the spiny dogfish. Most of these cells were located in the 'intestinal' lobe of the pancreas; only occasional cells were observed in the 'splenic' lobe. The gastrin/CCK-like immunoreactive cells were often co-localized with the 'classical' pancreas hormones (insulin, glucagon and somatostatin). Radioimmunoassay of water extracts with a C-terminally directed antiserum revealed high levels of immunoreactive material in the intestinal part (48.6 +/- 19.9 pmol/g) and lower levels (4.5 +/- 0.6 pmol/g) in the splenic part. Acetic acid extracts of the intestinal lobe contained low levels (6.8 +/- 3.3 pmol/g) of gastrin/CCK-like immunoreactivity, whereas corresponding extracts of the splenic part showed no immunoreactivity. When the extracts were subjected to DEAE ion-exchange chromatography the gastrin/CCK-like peptides eluted as a major peak. After Sephadex gel filtration, pooled immunoreactive material from the main DEAE chromatographic peak eluted at a position close to that of CCK4. Further characterization by ion-exchange and reversed-phase HPLC showed that, in general, the immunoreactive material behaved like the shorter forms of the gastrin/CCK family (CCK4/G5 and CCK8/Cae 3-10).
 ...
PMID:Endocrine cells with gastrin/cholecystokinin-like immunoreactivity in the pancreas of the spiny dogfish, Squalus acanthias. 1250 16

Somatostatin is important in the regulation of diverse neuroendocrine functions. Based on bioinformatic analyses of evolutionarily conserved sequences, we predicted another peptide hormone in pro-somatostatin and named it neuronostatin. Immuno-affinity purification allowed the sequencing of an amidated neuronostatin peptide of 13 residues from porcine tissues. In vivo treatment with neuronostatin induced c-Fos expression in gastrointestinal tissues, anterior pituitary, cerebellum, and hippocampus. In vitro treatment with neuronostatin promoted the migration of cerebellar granule cells and elicited direct depolarizing actions on paraventricular neurons in hypothalamic slices. In a gastric tumor cell line, neuronostatin induced c-Fos expression, stimulated SRE reporter activity, and promoted cell proliferation. Furthermore, intracerebroventricular treatment with neuronostatin increased blood pressure but suppressed food intake and water drinking. Our findings demonstrate diverse neuronal, neuroendocrine, and cardiovascular actions of a somatostatin gene-encoded hormone and provide the basis to investigate the physiological roles of this endogenously produced brain/gut peptide.
 ...
PMID:Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions. 1875 29


<< Previous 1 2 3