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)

The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.
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PMID:Decrease in alkaline secretion during duodenal ulceration induced by mepirizole in rats. 673 82

The effects of porcine vasoactive intestinal peptide on the acid and pepsin secretions from denervated gastric pouches and innervated stomach were studied in conscious cats both in basal conditions and after stimulation with pentagastrin, histamine, or a liver meal. In contrast with the well-known inhibitory effect of vasoactive intestinal peptide on acid and pepsin secretions in dogs, the peptide induced in cats an increase of the acid and pepsin responses to pentagastrin and an increase of the gastric mucosal blood flow as determined by aminopyrine clearance. Vasoactive intestinal peptide similarly enhanced the acid and pepsin responses to a liver meal in spite of a significant inhibition of the postprandial release of gastrin. The peptide increased the pepsin response but slightly decreased the acid response to histamine. Thus in cats, porcine vasoactive intestinal peptide consistently stimulates pepsin secretion and potentiates the meal- and pentagastrin-induced acid responses.
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PMID:Effect of vasoactive intestinal peptide on gastric secretion in the cat. 680 39

The enteric nervous system contains neurones that are intrinsic to the gastrointestinal tract and the axons of extrinsic neurones. More than 30 functional types of neurone are present and about 25 different possible neurotransmitters have been identified in enteric neurones. Most neurones utilize several transmitters; amongst the transmitters of an individual neurone, one is usually a primary transmitter and other substances are subsidiary transmitters or neuromodulators. The primary transmitter is the substance that has the major role in acutely changing the excitability of the innervated cell. Current evidence indicates that primary transmitters are strongly conserved; that is, the same substance will be the neurotransmitter in functionally equivalent neurones in different regions of the gastrointestinal tract and in different species. In contrast, subsidiary transmitters and neuromodulators of equivalent neurones in different regions are not necessarily the same. Only about seven of the approximately 25 enteric neurotransmitters are known to be primary transmitters. Acetylcholine is the primary transmitter of vagal and pelvic preganglionic neurones, of enteric interneurones, of one class of secretomotor neurone in the intestine and of motor neurones controlling gastric acid secretion. Acetylcholine and tachykinins are co-primary transmitters of muscle motor neurones, with acetylcholine appearing to have the greater role. Tachykinins are probably primary transmitters of enteric sensory neurones at neuroneuronal synapses. Serotonin may also be a transmitter to neurones in the enteric ganglia. Nitric oxide appears to be the usual primary transmitter of enteric inhibitory motor neurones to the muscle. ATP and vasoactive intestinal peptide are subsidiary transmitters of these neurones, although in some regions they may have a primary transmitter role. Vasoactive intestinal peptide is the primary transmitter of non-cholinergic secretomotor neurones. Gastrin releasing peptide is the primary transmitter of motor neurones to gastrin cells. Noradrenaline is the primary transmitter of sympathetic neurones that supply the intestine.
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PMID:Gastrointestinal neurotransmitters. 790 63

Interactions between growth factor receptor systems may be important in the regulation of cell growth. The proliferation of pancreatic tumor AR42J cells has been shown to be stimulated by Epidermal growth factor (EGF) and gastrin and inhibited by somatostatin. To analyze the interaction between these different peptides, we explored the influence of EGF and gastrin on the somatostatin receptors. Treatment of AR42J cells with 10 nM EGF or gastrin for 24 hr increased specific binding of [125I] Tyr3SMS to 131 and 147% of that in control cells, respectively. The effect of peptides on [125I]Tyr3SMS binding was time- and dose-dependent, with half-maximal effect at 0.2 +/- 0.03 nM EGF and 0.3 +/- 0.15 nM gastrin. Scatchard plots revealed an increase in somatostatin receptor number of 27 and 80% after 48 hr of treatment with EGF and gastrin, respectively, without any change in receptor affinity. The increase in somatostatin receptor density was accompanied by the enhancement of biological responses to somatostatin. In cells pretreated with EGF or gastrin, the potency of somatostatin for inhibiting vasoactive intestinal peptide-stimulated cAMP content was increased 2-fold as that of somatostatin analog, SMS, for inhibiting cell proliferation. Furthermore, the efficiency of SMS as antiproliferative agent was greatly increased. Vasoactive intestinal peptide or forskolin did not modify [125I]Tyr3SMS binding of control or treated cells. The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) did not affect [125I]Tyr3SMS binding. On the other hand, cycloheximide completely blocked the increase in [125I]Tyr3SMS binding induced by EGF and gastrin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. 805 63

Vasoactive intestinal peptide (VIP) has been localized within the suprachiasmatic nucleus of the hypothalamus (SCN) and appears to play an important role in the entrainment of circadian rhythms with the light-dark (LD) cycle. The spontaneously hypertensive rat (SHR), an inbred strain used extensively in research on primary hypertension, has significantly more VIP mRNA in its brain than normotensive Wistar-Kyoto control (WKY) rats. Because VIP levels are abnormally high in SHR rats the present study examined whether the mechanisms controlling circadian rhythms are also altered in SHR rats. When entrained to a 24 h LD cycle, SHR rats began their wheel-running rhythm approximately 1.5 h earlier than WKY controls. SHR rats re-entrained to a phase delay in the LD cycle more slowly than did WKY rats, but tended to re-entrain to a phase advance more rapidly. The free-running period of SHR rats in both constant light and constant dark was significantly shorter than that of WKY rats. In SHR rats, phase delays produced by 1-h pulses of light were less than one-half the magnitude of the delays seen in WKY rats; however, the phase advances were nearly twice that of WKY rats. Using in situ hybridization, the SCN levels of mRNA encoding VIP were found to be significantly greater in SHR rats, but the mRNA levels of another peptide important for entrainment, gastrin releasing peptide, did not differ between SHR and WKY rats. These data indicate that the mechanisms controlling circadian rhythms in SHR rats differ significantly from those controlling rhythms in WKY rats and that VIP mRNA is significantly elevated within the SCN of SHR rats. The role of VIP in the entrainment of circadian rhythms is discussed.
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PMID:The control of circadian rhythms and the levels of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus are altered in spontaneously hypertensive rats. 820 75

Peptidergic influences have been implicated in the control of tone in human arteries. We have examined the response of human gastroepiploic arteries (GEA) and internal mammary arteries (IMA) to three vasoactive peptides in vitro. Vasoactive intestinal peptide (VIP, 10(-11) to 3 x 10(-7) M) elicited relaxations in the GEA and IMA [maximum generated response (Emax) 74.6 +/- 9.4 and 56.5 +/- 7.7%, respectively] that were significantly reduced after removal of endothelium. NG-monomethyl-L-arginine (L-NMMA) and indomethacin partially inhibited the response of the GEA to VIP (P < 0.05). In the IMA, VIP-induced relaxation was significantly attenuated by L-NMMA but not indomethacin. Bombesin (10(-10) to 3 x 10(-6) M) produced endothelium-dependent relaxation selectively in the GEA, which was only inhibited by indomethacin (Emax reduced from 59.0 +/- 10.0 to 12.8 +/- 4.9%, P < 0.001). Bombesin elicited a weak endothelium-independent constriction in the IMA, giving 12.7 +/- 1.2% of the response to 90 mM KCl. Gastrin (10(-10) to 3 x 10(-7) M) had no effect on IMA segments but induced a relaxation of 40.0 +/- 3.2% in the GEA via a direct action on the smooth muscle. It is concluded that human GEA and IMA exhibit heterogenous responses to VIP, bombesin, and gastrin that may have important physiological and clinical implications.
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PMID:Different responses of the human gastroepiploic and internal mammary arteries to vasoactive peptides. 844 70

Unlike in rodents, CCK has not been established as a physiological regulator in avian exocrine pancreatic secretion. In the isolated duck pancreatic acini, 1 nM CCK was required for stimulation of amylase secretion, maximal effect being achieved at 10 nM; picomolar CCK was without effect. Vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating peptide (PACAP) receptor (VPAC) agonists PACAP-38 and PACAP-27 (10(-12)-10(-7) M) alone had no effect, but made picomolar CCK effective. VPAC agonist VIP 10(-10)-10(-7) M stimulated amylase secretion marginally, but made CCK 10(-12)-10(-10) M effective also. PACAP-27 and VIP both shifted the maximal CCK concentration from 10(-8) to 10(-9) M. This sensitizing effect was mimicked by forskolin. CCK dose dependently induced intracellular Ca2+ concentration ([Ca2+]i) oscillations. PACAP-38 (1 nM), PACAP-27 (1 nM), VIP (10 nM), or forskolin (10 microM) alone did not stimulate [Ca2+]i increase, neither did they modulate CCK (1 nM)-induced oscillations; but when they were added to cells simultaneously exposed to subthreshold CCK (10 pM), calcium spikes emerged. Amylase secretion induced by the simultaneous presence of 10 pM CCK and VPAC agonists was completely blocked by removing extracellular calcium, but the protein kinase C inhibitor staurosporine (1 microM) was without effect. CCK (10 nM)-induced secretion was inhibited by CCK1 receptor antagonist FK480 (1 microM). Gastrin from 10(-12) to 10(-6) M did not stimulate amylase secretion nor did it (100 nM) induce [Ca2+]i increase. The above data suggest that duck pancreatic acini possess both CCK1 and VPAC receptors; simultaneous activation of both is required for each to play a physiological role.
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PMID:Mutual dependence of VIP/PACAP and CCK receptor signaling for a physiological role in duck exocrine pancreatic secretion. 1294 31

Vasoactive intestinal peptide (VIP) neurons constitute a large group in the suprachiasmatic nucleus (SCN) and it is thought that they are involved in the generation and entrainment of circadian rhythm. We have characterized these VIP-expressing neurons in rat SCN by their ability to induce the mammalian Period1 (Per1) gene in response to light exposure, innervation of retinal afferents, day-night variations in VIP mRNA, and coexpression of gastrin releasing peptide (GRP). VIP neurons in the ventrolateral SCN (SCNVL) were subdivided into two groups, light-evoked Per1-inducible main SCNVL (SCNVLmain) and non-Per1-inducible medially located SCNVL (SCNVLmed). Retinal innervation was abundant in the SCNVLmain but nearly absent in the SCNVLmed. Day-night variation in VIP mRNA expression level was observed in the SCNVLmain but not in the SCNVLmed. GRP mRNA was seen in rarely SCNVLmed but abundant in SCNVLmain, where some neurons coexpressed VIP mRNA. These findings indicate that VIP neurons in the SCN can be divided into two topographically and functionally distinct groups.
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PMID:Two types of VIP neuronal components in rat suprachiasmatic nucleus. 1464 89

Although the enterochromaffin (EC) cell is one of the primary neuroendocrine regulatory cells of the small intestine, the lack of a purified cell system has precluded characterization of the cell and limited precise physiological evaluation. We developed methodology to obtain a pure population of Mastomys ileal EC cells, evaluated their functional regulation, and defined the transcriptome. Mastomys ilea were everted, end ligated, pronase-collagenase digested, and Nycodenz gradient centrifuged, and EC cells were collected by fluorescence-activated cell sorting (FACS) of acridine orange-labeled cells. Enrichment was confirmed by immunostaining of tryptophan hydroxylase and chromogranin A, specific EC cell markers, serotonin content, EC cell marker gene expression, and electron microscopy. Pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin, and gastrin receptor expression was determined by real-time RT-PCR. Live post-FACS-sorted cells were cultured, and the effects of forskolin, isoproterenol, acetylcholine, GABAA, PACAP-38, and gastrin on serotonin secretion were measured by ELISA. GeneChip Affymetrix profiling of FACS-sorted cells was undertaken to obtain the EC cell transcriptome. FACS produced a >70-fold enrichment of EC cells with a serotonin content of 240 +/- 22 ng/mg protein. Preparations were 99 +/- 0.7% pure by immunostaining for tryptophan hydroxylase. Vasoactive intestinal peptide/PACAP receptor 1 (VPAC1) and somatostatin receptor 2 were present, whereas PACAP receptor 1 (PAC1) and CCK2 receptors were undetectable. Forskolin, isoproterenol, and PACAP-38 stimulated serotonin secretion at EC50 values of 5 x 10(-10), 4.5 x 10(-10), and 1.2 x 10(-9) M, respectively. Isoproterenol stimulated cAMP levels by approximately 3.5 +/- 0.62-fold vs. unstimulated cells (EC50 of approximately 10(-9) M). Octreotide, acetylcholine, and GABAA inhibited serotonin secretion with IC50 values of 3 x 10(-11), 3 x 10(-10), and 2.9 x 10(-10) M, respectively. Gastrin had no effect on serotonin secretion. The naive EC cell transcriptome revealed highly expressed EC cell marker genes, the absence of marker genes for other small intestinal cell types, and a receptor profile that included cholinergic, adrenergic, dopaminergic, serotoninergic, GABAergic, and prostaglandin receptors. We were able to isolate homogeneous preparations (>99%) of live ileal EC cells and demonstrated regulation of serotonin secretion as well as established the normal EC cell transcriptome. Application of this methodology to normal and diseased human ileum will facilitate the elucidation of the pathophysiology of EC cells.
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PMID:Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells. 1645 86


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