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)

Peptides release histamine from enterochromaffin-like (ECL) cells because of elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) by either receptor-operated or voltage-dependent Ca(2+) channels (VDCC). To determine whether VDCCs contribute to histamine release stimulated by gastrin or pituitary adenylate cyclase-activating polypeptide (PACAP), the presence of VDCCs and their possible modulation by peptides was investigated in a 48-h cultured rat gastric cell population containing 85% ECL cells. Video imaging of fura 2-loaded cells was used to measure [Ca(2+)](i), and histamine was assayed by RIA. Cells were depolarized by increasing extracellular K(+) concentrations or by 20 mM tetraethylammonium (TEA(+)). Cell depolarization increased transient and steady-state [Ca(2+)](i) and resulted in histamine release, dependent on extracellular Ca(2+). These K(+)- or TEA(+)-dependent effects on histamine release from ECL cells were coupled to activation of parietal cells in intact rabbit gastric glands, and L-type channel blockade by 2 microM nifedipine inhibited 50% of [Ca(2+)](i) elevation and histamine release. N-type channel blockade by 1 microM omega-conotoxin GVIA inhibited 25% of [Ca(2+)](i) elevation and 14% of histamine release. Inhibition was additive. The effects of 20 mM TEA(+) were fully inhibited by 2 microM nifedipine. Both classes of Ca(2+) channels were found in ECL cells, but not in parietal cells, by RT-PCR. Nifedipine reduced PACAP-induced (but not gastrin-stimulated) Ca(2+) entry and histamine release by 40%. Somatostatin, peptide YY (PYY), and galanin dose dependently inhibited L-type Ca(2+) channels via a pertussis toxin-sensitive pathway. L-type VDCCs play a role in PACAP but not gastrin stimulation of histamine release from ECL cells, and the channel opening is inhibited by somatostatin, PYY, and galanin by interaction with a G(i) or G(o) protein.
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PMID:Role of neuropeptide-sensitive L-type Ca(2+) channels in histamine release in gastric enterochromaffin-like cells. 1060 Aug 25

Prolactinoma is the most common type of primary pituitary tumors. It occurs more frequently in women than in men. Dopaminergic agonists are effective in the shrinkage of prolactin-secreting pituitary tumor and are preferred in some patients. However, pituitary radiotherapy may enable the long-term removal of prolactin-secreting tumor cells. Recent evidence suggests that prolactinoma is a heterogeneous disorder with complicated and multifactorial etiology and pathogenesis. Apparently, a thorough understanding of prolactinoma tumorigenesis would be important. To facilitate investigations on tumorigenesis of prolactinoma, animal models for prolactinomas have been developed. These models have expedited our progress in the recent years. Many researchers consider the F(344) rat to be the most sensitive strain of rats to estrogen (E(2))-induced prolactinoma formation. Nonetheless, E(2) treatment for 60 days also induces the formation of pituitary prolactin-secreting adenoma in male Sprague-Dawley (SD) rats. Evidently, the SD rat is also a good animal for prolactinoma investigations. Following E(2) implantation, prolactinomas developed in the eutopic adenohypophysis in situ and/or ectopic pituitary grafted under the renal capsule in SD rats. These observations favor the hypothesis that prolactinoma growth is the result of pathological changes in the adenohypophysis and/or hypothalamus. In the latter case, abnormal release of hypothalamic dopamine, GABA, or brain-gut peptides (such as cholecystokinin, vasoactive intestinal polypeptide, galanin, angiotensin, opioid peptide, gastrin, gastrin-releasing peptide, pancreatic polypeptide, and adrenocorticotropic hormone) results in some of the pathological changes that may lead to hyperprolactinemia and/or prolactinoma development. Dysregulation of prolactin synthesis and secretion may be the result of prolactin gene modulation. In E(2)-induced rat prolactinomas, prolactin mRNA contents and the expression of some proto-oncogenes, e.g. c-myc and c-ras, TGFalpha and TGFbeta1 mRNA were significantly changed. The above findings are consistent with results in human prolactinoma development. In addition, in rats abnormal expression of the prolactin gene was correlated with hypomethylated status of CpG sites in exons 1, 2 and 4 of the prolactin gene, as well as the increase in hypersensitive sites to DNase 1 in the encoding region of the prolactin gene. In E(2)-treated rats, a point mutation with a base substitution from cytidine (C) to adenine (A) was found at the -36-bp site of the proximal promoter of the prolactin gene in eutopic pituitary prolactinomas, but no change was observed in the same sequence of the prolactin gene in ectopic prolactinoma. The association of a base substitution with the hyperexpression of the prolactin gene in eutopic prolactinomas suggests that different mechanisms may mediate the formation of eutopic and ectopic prolactin-secreting tumors. Melatonin decreases the expression of the prolactin gene in vitro suggesting that this pineal hormone may be a potential anticarcinogen in vivo. It has also been shown that MT(2) (Mel(1b)) melatonin receptors are expressed in anterior pituitary cells. The use of melatonin as a preventive or therapeutic drug for prolactinomas should be further investigated. In summary, improved knowledge on tumorigenesis of prolactinomas, especially in the rat model, was noted. These E(2)-induced rat prolactinoma models would facilitate future investigations, and expected results shall be fruitful and exciting for the development of future drug designs for the prevention and/or treatment of prolactin-secreting pituitary tumors.
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PMID:Pituitary prolactin-secreting tumor formation: recent developments. 1068 32

The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.
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PMID:Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy. 1070 47

The pancreatic islets are richly innervated by parasympathetic, sympathetic and sensory nerves. Several different neurotransmitters are stored within the terminals of these nerves, both the classical neurotransmitters, acetylcholine and noradrenaline, and several neuropeptides. The neuropeptides, vasoactive intestinal polypeptide, pituitary adenlyate cyclase activating polypeptide and gastrin releasing peptide are constituents of the parasympathetic nerves, whereas the neuropeptides galanin and neuropeptide Y are localised to sympathetic nerve terminals. Furthermore, the neuropeptide calcitonin gene-related peptide is localised to sensory nerves and cholecystokinin is also an islet neuropeptide, although the nature of the cholecystokinin nerves is not established. Stimulation of the autonomic nerves and treatment with neurotransmitters affect islet hormone secretion. Thus, insulin secretion is stimulated by parasympathetic nerves or their neurotransmitters and inhibited by sympathetic nerves or their neurotransmitters. The islet autonomic nerves seem to be of physiological importance in mediating the cephalic phase of insulin secretion, in synchronising the islets to function as a unit allowing oscillations of islet hormone secretion, and in optimising islet hormone secretion during metabolic stress, e.g. hypoglycaemia and neuroglycopenia. The autonomic nerves could also be involved in the islet adaptation to insulin resistance with possible implication for the development of glucose intolerance and Type II (non-insulin-dependent) diabetes mellitus. It is concluded that islet innervation, through the contribution of all branches of the autonomic nerves and several different neurotransmitters is of importance both for the physiology and pathophysiology of the islets.
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PMID:Autonomic regulation of islet hormone secretion--implications for health and disease. 1081 32

In vertebrates, the peptides cholecystokinin (CCK), neuropeptide Y, galanin, and bombesin are known to be involved in the control of food intake. We report here that insect sulfakinins, peptides which display substantial sequence similarities with the vertebrate gastrin/CCK peptide family, significantly inhibit food uptake in fifth instar nymphs of the locust, Schistocerca gregaria. Upon injection of Lom-sulfakinin, a neuropeptide present in the corpus cardiacum of locusts, food intake was significantly reduced in a dose-dependent manner within a fixed 20 min time period. The induced effect ranged from 13% inhibition (10 pmol of injected peptide) to over 50% inhibition at 1 nmol. Other naturally occurring sulfakinins from different insect species also elicited this satiety effect. Analogous to the satiety effect of CCK in vertebrates, the sulfate group is required for activity. No effect on the palptip resistance was found after injection with sulfakinin. Therefore it seems unlikly that sulfakinins reduce food intake by decreasing the sensitivity of the taste receptors.
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PMID:Sulfakinins reduce food intake in the desert locust, Schistocerca gregaria. 1084 44

ECL cells are endocrine/paracrine cells in the oxyntic mucosa. They produce, store and secrete histamine and chromogranin A-derived peptides such as pancreastatin. The regulation of ECL-cell secretion has been studied by several groups using purified ECL cells, isolated from rat stomachs. Reports from different laboratories often disagree. The purpose of the present study was to re-evaluate the discrepancies by studying histamine (or pancreastatin) secretion from standardized preparations of pure, well-functioning ECL cells. Cells from rat oxyntic mucosa were dispersed by pronase digestion, purified by repeated counter-flow elutriation and subjected to density gradient centrifugation. The final preparation consisted of more than 90% ECL cells (verified by histamine and/or histidine decarboxylase immunocytochemistry). They were maintained in primary culture for 48 h before they were exposed to candidate stimulants and inhibitors for 30 min after which the medium was collected for determination of mobilized histamine (or pancreastatin). Gastrin-17 and sulphated cholecystokinin octapeptide (CCK-8s) raised histamine secretion 4-fold, the EC(50) for both peptides being around 100 pM. The neuropeptide pituitary adenylate cyclase activating peptide (PACAP-27) (5-fold increase) and the related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) (3-fold increase) mobilized histamine with similar potency (EC(50) ranging from 80 to 140 pM). Adrenaline, isoprenaline and terbutaline stimulated secretion by activating a beta2 receptor subtype, while acetylcholine and carbachol were without effect. Secretion experiments were invariably run in parallel with a gastrin standard curve. Somatostatin, prostaglandin E2 (PGE2) and the PGE1 congener misoprostol inhibited PACAP- and gastrin-stimulated secretion by more than 90%, with IC(50) values ranging from 90-720 (somatostatin) to 40-200 (misoprostol) pM. The neuropeptide galanin inhibited secretion by 60-70% with a potency similar to that of somatostatin. Proposed inhibitors such as peptide YY, neuropeptide Y and the cytokines interleukin 1-beta and tumor necrosis factor alpha induced at best a moderate inhibition of gastrin- or PACAP-stimulated secretion at high concentrations, while calcitonin gene-related peptide, pancreatic polypeptide and histamine itself were without effect. Inhibition of gastrin- or PACAP-stimulated secretion was routinely compared to a somatostatin standard curve. In conclusion, gastrin, PACAP, VIP/PHI and adrenaline stimulated secretion. Somatostatin and PGE2 were powerful inhibitors of both gastrin- and PACAP-stimulated secretion; although equally potent, galanin was less effective than somatostatin and PGE2.
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PMID:Neurohormonal regulation of secretion from isolated rat stomach ECL cells: a critical reappraisal. 1116 53

The current view of the control of food intake involves a central feeding system in the hypothalamus receiving input from peripheral systems. The presence of food in the gut stimulates the release of several regulatory peptides that control gut motility and secretion. Some of these peptides also act as feedback satiety signals, responsible for termination of a meal. Among the regulatory peptides suggested as peripheral satiety signals are cholecystokinin and gastrin releasing peptide. A more long-term peripheral regulation of food intake has also been postulated and leptin has been suggested as a regulator of food intake. Several regulatory peptides mediate orexigenic or anorexigenic effects in the central feeding system. Neuropeptide Y and galanin both act centrally and stimulate the intake of food, while corticotropin releasing factor reduces food intake. At present, most information about the regulation of food intake is gained from mammalian studies and these findings are used as a base for a discussion on the current knowledge of how regulatory peptides control appetite in non-mammalian vertebrates.
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PMID:Regulatory peptides and control of food intake in non-mammalian vertebrates. 1124 39

The ECL cells control parietal cells by releasing histamine in their immediate vicinity. Gastrin and pituitary adenylate cyclase-activating peptide (PACAP) stimulate histamine secretion from isolated ECL cells, while somatostatin and galanin inhibit stimulated secretion. Prostaglandin E2 and related prostaglandins likewise suppress ECL-cell histamine secretion. Conceivably, that is how they inhibit acid secretion. In the present study, we examined if prostaglandin E2 can be generated by isolated ECL cells. Rat stomach ECL cells were purified (>90% purity) by counterflow elutriation and gradient centrifugation and cultured for 48 h. ECL cell stimulants (gastrin and PACAP) and inflammatory agents (interleukin-1 beta, tumor necrosis factor-alpha and bradykinin) were tested for their ability to induce prostaglandin E2 accumulation (24-h incubation), measured by radioimmunoassay. Gastrin and PACAP did not affect prostaglandin E2 accumulation but interleukin-1 beta (300 pg/ml), tumor necrosis factor-alpha (10 ng/ml) and bradykinin (1 microM) induced a 2- to 3-fold increase in the amount of prostaglandin E2 accumulated. While the combination of interleukin-1 beta and bradykinin induced a 9-fold increase, the combination interleukin-1 beta+tumor necrosis factor-alpha and bradykinin + tumor necrosis factor-alpha induced additive effects only. The combination of interleukin-1 beta + tumor necrosis factor-alpha + bradykinin did not induce a greater effect than interleukin-1 beta + bradykinin. The effect of interleukin-1 beta + bradykinin was abolished by adding 10 nM hydrocortisone (suppressing phospholipase A2 and cyclooxygenase) or 1 microM indomethacin (inhibiting cyclooxygenase). Incubating ECL cells in the presence of interleukin-1 beta+bradykinin for 24 h reduced their ability to secrete histamine in response to gastrin. The inhibitory effect was reversed by 1 microM indomethacin. Also, increasing the concentrations of hydrocortisone in the medium resulted in an enhanced gastrin-stimulated histamine secretion. Hence, the previously described acid-inhibiting effect of inflammatory agents may be explained by inhibition of ECL-cell histamine mobilization, consequent to enhanced formation of prostaglandin E2 by cells in the oxyntic mucosa, including the ECL cells themselves.
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PMID:Isolated rat stomach ECL cells generate prostaglandin E(2) in response to interleukin-1 beta, tumor necrosis factor-alpha and bradykinin. 1129 Mar 77

Gastrointestinal transit (GI) in the nonobese diabetic (NOD) mouse, an animal model of human diabetes type 1, was examined in animals with short- (duration 1-5 days) and long-term (duration 28-35 days) diabetes. Blood glucose level, serum insulin concentration, and gut neuroendocrine peptide content were also measured. GI was significantly rapid in NOD mice with long-term diabetes (LTD), but was not correlated with blood glucose level, serum insulin concentration, or pancreatic insulin content. GI was correlated with duodenal secretin content, but not with the content of other neuroendocrine peptides in the different segments investigated. Whereas antral vasoactive intestinal peptide (VIP) content in NOD mice with LTD was significantly higher, colonic VIP was lower in NOD mice with short-term diabetes (STD). In the duodenum, whereas the concentration of secretin in NOD mice with both STD and LTD was lower, the gastrin content was higher. Duodenal somatostatin content in NOD mice with LTD was lower. In colon, the content of galanin in NOD mice with LTD was higher than in controls. The decreased content of secretin may be among the factors that cause rapid GI in NOD mice with LTD. Changes in the antral content of VIP, duodenal somatostatin, and colonic galanin in NOD mice with LTD may cause low intestinal secretion and, together with rapid GI, give rise to diarrhoea, which is a common symptom in diabetes.
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PMID:Gastrointestinal transit in nonobese diabetic mouse: an animal model of human diabetes type 1. 1156 57

The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of the mammalian circadian timing system. The SCN is composed of two anatomically and functionally distinct subdivisions, designated core and shell, which can be distinguished on the basis of their chemoarchitecture and connections in the rat. In the present study, we examine the intrinsic organization and the afferent and efferent connections of the mouse SCN using immunocytochemistry and ocular injections of cholera toxin. Neurons of the SCN shell contain GABA, calbindin (CALB), arginine vasopressin (AVP), angiotensin II (AII) and met-enkephalin (mENK), and receive input from galanin (GAL) and vasoactive intestinal polypeptide (VIP) immunoreactive fibers. Neurons of the SCN core synthesize GABA, CALB, VIP, calretinin (CALR), gastrin releasing peptide (GRP), and neurotensin (NT), and receive input from the retina and from fibers that contain neuropeptide Y (NPY) and 5-hydroxytryptamine (5HT). Fibers projecting from SCN neurons that are immunoreactive for AVP and VIP exhibit a characteristic morphology, and project to the lateral septum, a series of medial hypothalamic areas extending from the preoptic to the posterior hypothalamic area and to the paraventricular thalamic nucleus. The organization of the mouse SCN, and its connections, are similar to that in other mammalian species.
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PMID:Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. 1159 5


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