Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive intestinal peptide (VIP) is a potent and efficient stimulator of adenosine 3':5'-cyclic monophosphate (cAMP) accumulation in a human colon carcinoma cell line, HT 29. cAMP accumulation is sensitive to a concentration of VIP as low as 3x10(-12) M. Maximum VIP-induced cAMP levels were observed with 10(-9) M VIP and are about 200 times above the basal levels. Half-maximum cAMP production was obtained at 3x10(-10) M VIP. (125)I-Labeled VIP was found to bind to HT 29 cells; this binding was competitively inhibited by concentrations of unlabeled VIP between 10(-10) and 10(-7) M. Half-maximum inhibition of binding was observed with 2x10(-9) M VIP. Secretin also stimulated cAMP accumulation in HT 29 cells, but its effectiveness was 1/1000 that of VIP. The other peptides tested at 10(-7) M, such as insulin, glucagon, bovine pancreatic polypeptide, somatostatin, octapeptide of cholecystokinin, neurotensin, and substance P, did not stimulate cAMP accumulation. Prostaglandin E(1) and catecholamines stimulated cAMP production but were 1/2.3 and 1/5.5 as efficient as VIP, respectively. Another malignant cell line from the gut, the human rectal tumor cell line HRT 18, is also sensitive to VIP. In HRT 18 cells, VIP stimulated cAMP accumulation with a maximal effect at 10(-8) M; half-maximum stimulation was observed at about 10(-9) M. These results demonstrate the presence of VIP receptors in two malignant human intestinal cell lines (HT 29 and HRT 18) in culture and provide a model for studying the action of VIP on cell proliferation.
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PMID:Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'-cyclic monophosphate accumulation in gut carcinoma cell lines in culture. 20 77

1. The vascular bed of the submandibular gland in situ was perfused with blood through the glandular artery at a constant pressure in anesthetized dogs. All drugs were administered intra-arterially. 2. Vasoactive intestinal peptide (VIP), secretin and acetylcholine produced a dose-dependent increase in blood flow through the artery (vasodilatation) but glucagon was almost ineffective. 3. Dose-blood flow response curves for VIP and secretin were parallel, and VIP was about 100 times as potent as secretin on a molar basis. Dose-blood flow response curves for acetylcholine were flatter than those for VIP and secretin. Acetylcholine was approximately as potent as secretin on a molar basis. 4. No tachyphylaxis developed to the vasodilator action of VIP. 5. The vasodilator responses to VIP and to electrical stimulation of the chordolingual nerve were scarcely modified by (-)-hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine. 6. VIP, secretin and glucagon were ineffective in eliciting salivary secretion. 7. The possibility that VIP is released from parasympathetic vasodilator nerves and mediates the atropine-resistant vasodilatation in the dog submandibular gland is discussed.
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PMID:Assessment of the effects of vasoactive intestinal peptide (VIP) on blood flow through and salivation of the dog salivary gland in comparison with those of secretin, glucagon and acetylcholine. 43 91

The duodenums of opossums and cats were cut into strips 2 mm wide and 2-2.5 cm long. Strips cut in the oral-caudal axis were called longitudinal strips; those cut at 90 degrees to that axis were called circular strips. Cholecystokinin (CCK) and cerulein stimulated phasic contractions of circular muscle of opossum duodenum, but had no effect on the longitudinal muscle. The effect of CCK was not blocked by tetrodotoxin (10(-7)M), indicating a direct muscle stimulation. CCK had no effect of both muscle layers of the cat duodenum. Vasoactive intestinal peptide raised tension in longitudinal muscle, but reduced tension in circular muscle of opossum duodenum. Glucagon slightly reduced tension in both longitudinal and circular muscle of opossum duodenum. It also inhibited contractions of circular muscle caused by acetylcholine. Pentagastrin and secretin had no effect on either muscle layer in either species. These findings suggest that the circular and longitudinal muscle layers of the duodenum respond differently to at least some gastrointestinal hormones. Also, there is species variation in response to gastrointestinal hormones.
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PMID:Effects of some gastrointestinal hormones on two muscle layers of duodenum. 62 51

This paper deals with several new findings regarding the trophic action of gastrointestinal hormones. Naturally occurring gastrins (G-17 I, G-17 II, G-34 II) stimulated DNA synthesis and increased total DNA content of gastric mucosa. These were several times more potent than pentagastrin on a molar basis. In a survey of various tissues from the gastrointestinal tract, pentagastrin exerted trophic effects on mucosa of the oxyntic gland area, duodenum, and colon; it had no effect on the esophagus, antrum, or diaphragm. Maximal stimulation (200% of control) of colonic DNA synthesis was produced by 250 mug of pentagastrin per kg. Vasoactive intestinal peptide did not stimulate DNA synthesis when given alone and inhibited the trophic effect of pentagastrin when administered simultaneously. Glucagon stimulated DNA synthesis in both colon and oxyntic gland mucosa to 40% of the increase caused by pentagastrin and did not inhibit the effects of pentagastrin when administered concurrently.
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PMID:New aspects of the trophic action of gastrointestinal hormones. 83 37

Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides.
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PMID:A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. 132 27

Vasoactive intestinal peptide (VIP) stimulated cyclic AMP production in rat peritoneal macrophages. The stimulatory effect of VIP was dependent on time, temperature and cell concentration, and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). At 15 degrees C, the response occurred in the 0.1-1000 nM range of VIP concentrations. Half maximal stimulation of cellular cyclic AMP (ED50) was obtained at 1.2 +/- 0.5 nM VIP, and maximal stimulation (about 3-fold basal level) was obtained between 100-1000 nM. The cyclic AMP system of rat peritoneal macrophages showed a high specificity for VIP. The order of potency observed in inducing cyclic AMP production was VIP greater than rGRF greater than hGRF greater than PHI greater than secretin. Glucagon, insulin, pancreastatin and octapeptide of cholecystokinin did not modify cyclic AMP levels at concentrations as high as 1 microM. The beta-adrenergic agonist isoproterenol increased the cyclic AMP production and show additive effect with VIP. Somatostatin inhibits the accumulation of cyclic AMP in the presence of both vasoactive intestinal peptide and isoproterenol. The finding of a VIP-stimulated cyclic AMP system in rat peritoneal macrophages, together with the previous characterization of high-affinity receptors for VIP in the same cell preparation, strongly suggest that VIP may be involved in the regulation of macrophage function.
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PMID:Stimulatory effect of vasoactive intestinal peptide (VIP) on cyclic AMP production in rat peritoneal macrophages. 137 99

Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands.
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PMID:Cloning and expression of the human vasoactive intestinal peptide receptor. 167 91

Vasoactive intestinal peptide, at different concentrations, was tested on the migration of leucocytes by using the sealed capillary migration test. Vasoactive intestinal peptide, at 10(-7)-10(-9)M, inhibited, while at 10(-12)-10(-14)M, stimulated mononuclear leucocyte migration. The migration of polymorphonuclear leucocytes was inhibited by vasoactive intestinal peptide at 10(-6)-10(-9)M, a stimulation was found at 10(-13)-10(-14)M. The inhibiting effect of vasoactive intestinal peptide on leucocyte migration was abolished when vasoactive intestinal peptide was split into C- and N-terminal fragments, while a stimulating effect was retained in the N-terminal fragment, at 10(-14)M, for mononuclear cells. Helodermin and peptide T, as well as two other members of the secretin-glucagon family, secretin and gastric inhibitory peptide, had no effect on the migration. When VIP antiserum was tested, it had an inhibiting effect, which was not seen with control serum, supporting a physiological effect of the lower vasoactive intestinal peptide concentrations. Vasoactive intestinal peptide seems to have dual effects on mononuclear and polymorphonuclear leucocyte migration and, generally, intact vasoactive intestinal peptide seems to be needed for these effects.
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PMID:Dual effects of vasoactive intestinal peptide (VIP) on leucocyte migration. 187 47

Vasoactive intestinal peptide (VIP) has been implicated as a physiological PRL-releasing factor; however, characterization of VIP receptors on normal pituitaries using radioligand-binding methods has been problematic. In this study we demonstrated specific receptors for VIP in anterior pituitary glands of female rats using HPLC-purified monoiodinated [Tyr(125I)10]VIP. Binding of VIP was reversible, saturable to receptor and radioligand, regulated by guanine nucleotides, and dependent on time and temperature. Scatchard analysis of competitive binding studies indicated high and low affinity binding sites, with equilibrium dissociation constants (Kd) of 0.19 +/- 0.03 and 28 +/- 16 nM, respectively. The corresponding maximum numbers of binding sites were 158 +/- 34 fmol/mg and 11.7 +/- 6.9 pmol/mg. Binding was specific, as peptides with structural homology to VIP were less than 100th as potent as VIP. The rank order of potency of the peptides tested was VIP greater than rat (r) peptide histidine isoleucine = human (h) PHI greater than rGRF greater than bovine GRF = porcine PHI = VIP-(10-28) greater than hGRF greater than secretin greater than apamin greater than glucagon. Radioligand binding was associated primarily with lactotrope-enriched fractions prepared by unit gravity sedimentation of dispersed anterior pituitary cells. VIP stimulated PRL release from cultured rat anterior pituitary cells, with an ED50 of 1 nM. These results, comprising the first identification of specific VIP receptors in normal rat anterior pituitary tissue using radioligand-binding methods, provide additional support for a biological role of VIP in lactotrope function.
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PMID:Receptors for vasoactive intestinal peptide in rat anterior pituitary glands: localization of binding to lactotropes. 215 75

Vasoactive intestinal peptide (VIP) receptors were identified in a human pancreatic carcinoma cell line by radioreceptor assay, including time course, dissociation study, competitive inhibition, and cross reactions with secretin and glucagon, both of which are hormones of the same family. Peak binding of 125I-VIP to the cells occurred at 20-30 min at 37 degrees C. Displacement curve showed an increasing inhibition of binding with increasing concentration of unlabeled VIP(inhibited by 95% at 1 microM of VIP). KD of VIP receptors was 1.68 x 10(-10)M, and the number of binding sites was 3.6 x 10(5)/cell. It was also shown that VIP was able to induce cAMP production in this cell line, indicating that the VIP receptors in this cell line were biologically active.
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PMID:[Vasoactive intestinal peptide receptor in a human pancreatic carcinoma cell line]. 216 37


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