Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigates interaction of bombesin receptors with heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and monomeric small molecular weight GTP-binding proteins (smg proteins), respectively, in plasma membranes (PM) of rat pancreatic acinar cells. Addition of bombesin to isolated PM stimulated the incorporation of the photoaffinity analogue [alpha-32P]GTP-gamma-azidoanilide into Gi proteins of 40-41 kDa and reduced the pertussis toxin-induced ADP ribosylation of three 40-41 kDa proteins, which had been previously identified as Gi1, Gi2, and Gi3 (30). In PM isolated from bombesin-prestimulated acinar cells, binding of [alpha-32P]-GTP to PM proteins of 21-22 kDa and of a monoclonal antibody against p21ras proteins was increased. Two-dimensional separation of PM proteins revealed the presence of 18 or 19 differently charged smg proteins. The p21ras proteins could be separated into two differently charged proteins with isoelectric points of 5.58 and 5.79. In microsomal membranes (MM), [alpha-32P]GTP binding to yet unidentified 21-22 kDa smg proteins was decreased compared with membranes from unstimulated acinar cells. The data suggest that Gi proteins as well as p21ras proteins are involved in bombesin receptor-mediated signal transduction in the PM. Furthermore, 21-22 kDa smg proteins in MM might play a role in bombesin-induced stimulation of intracellular pathways that lead to enzyme secretion from pancreatic acinar cells.
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PMID:Bombesin receptors interact with Gi and p21ras proteins in plasma membranes from rat pancreatic acinar cells. 132 28

The effects of somatostatin-14 and bombesin on [3H]inositol phosphate accumulation were studied in 24 h myo-[3H]inositol-prelabeled cultured rat acinar cells. Bombesin, 10 nM, stimulated basal formation of phosphatidyl monophosphate (InsP1), phosphatidyl 4,5-biphosphate (InsP2) and inositol 1,4,5-triphosphate (InsP3) by 128 +/- 5.2%, 147 +/- 10% and 155 +/- 5%, respectively. At 5 s, the ED50 value for InsP3 stimulation was 0.70 +/- 0.2 nM. This stimulation was partly blocked (64 +/- 0.04% inhibition) by 10 ng/ml Bordetella pertussis toxin. In contrast to bombesin, somatostatin, 10 nM, inhibited basal InsP1, InsP2 and InsP3 formation. At 5 s, the inhibition degree for InsP3 was 18 +/- 2.5% and the IC50s values 1 +/- 0.09 nM, 1 +/- 0.12 nM and 0.07 +/- 0.005 nM for InsP1, InsP2 and InsP3, respectively. Bombesin-stimulated InsP3 formation was also inhibited by somatostatin. At 5 s, the inhibition degree was 85 +/- 3.5% at 10 nM and the IC50 value, 0.10 +/- 0.05 nM. Furthermore, somatostatin inhibition of bombesin stimulation was partly blocked (66 +/- 4% inhibition) by Bordetella pertussis toxin. These data therefore suggest that the acinar pancreatic cells contain a somatostatin receptor exerting a negative control on basal and bombesin receptor-stimulated phosphatidyl inositol turnover.
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PMID:Somatostatin inhibition of phosphoinositides turnover in isolated rat acinar pancreatic cells: interaction with bombesin. 135 13

Human breast cancer cells have been recently reported to produce endothelin (ET) 1. To investigate the potential regulation of ET production in breast cancer cells, we have measured the release of ET-like immunoreactivity from the T47D cell line in response to various paracrine/endocrine factors. Bombesin (0.1 microM) and cortisol (1 microM) stimulated maximal respective increases in IR-ET release to 580 and 369% of basal values after 6 h. The responses to cortisol and bombesin were additive. The response to bombesin was dose dependent with a median effective dose around 1 nM and was inhibited by the receptor antagonist [Leu13-psi-CH2NH-Leu14]bombesin. Pretreatment of T47D cells with pertussis toxin had no effect on bombesin-induced inositol lipid hydrolysis but inhibited ET-like immunoreactivity release in response to bombesin in the presence of glucocorticoid, by 56%. ET-1 (10 nM) and insulin-like growth factor (10 ng/ml) stimulated modest separate increases in DNA synthesis in human breast fibroblasts of 35 and 71%, respectively, but together exhibited a strong synergistic response to 905% of control values. This in vitro study demonstrates the potential for bombesin and glucocorticoid to regulate ET production in human breast cancer cells, which may in turn have a paracrine influence on neighboring stromal cell function.
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PMID:Bombesin and glucocorticoids stimulate human breast cancer cells to produce endothelin, a paracrine mitogen for breast stromal cells. 155 Nov 9

The physiological regulation of intestinal proglucagon-derived peptide secretion has not been well studied. We have therefore used a fetal rat intestinal cell culture model to investigate the control of secretion of the gut glucagon-like immunoreactive (GLI) peptides by other intestinal regulatory peptides in vitro. Secretion of the intestinal GLI peptides was found to be stimulated in a dose-dependent fashion by the intestinal endocrine peptide, gastric inhibitory peptide (at greater than or equal to 10(-10) M, P less than 0.05), and by the neurocrine peptides, gastrin-releasing peptide (at greater than or equal to 10(-12) M, P less than 0.05), and calcitonin gene-related peptide (at greater than or equal to 10(-8) M, P less than 0.05). Gastrin-releasing peptide and its amphibian equivalent, bombesin were equipotent in stimulating GLI peptide secretion. In contrast, the endocrine and neurocrine intestinal somatostatin-related peptides, somatostatin-28 and -14, inhibited release of the GLI peptides, at concentrations of 10(-10) (P less than 0.01) and 10(-8) (P less than 0.01) M, respectively, with significant differences in potency between the two peptides detected at 10(-10) M (P less than 0.05). The inhibitory effects of both somatostatin-28 and -14 could be blocked by preincubation of the cells with pertussis toxin (P less than 0.05). Dose-dependent stimulation of gut GLI peptide secretion was also detected in response to treatment of cultured cells with sodium oleate (at 10(-4) M; P less than 0.05), or with the cholinergic agonist bethanecol (at greater than or equal to 100 microM; P less than 0.05). Other endocrine [cholecystokinin, glucagon, glucagon-like peptide-1(1-37), glucagon-like peptide-1(7-37), glucagon-like peptide-2, neurotensin, and peptide YY] and neurocrine (vasoactive intestinal peptide) peptides, and the synthetic glucocorticoid, dexamethasone, were without effect on secretion of the gut GLI peptides, at doses of 10(-12) to 10(-6) M. The results of the present study therefore demonstrate that secretion of the intestinal proglucagon-derived peptides is under the regulatory control of a wide variety of intestinal endocrine and neurocrine peptides, as well as nutrients (fats) and neurotransmitters (acetylcholine).
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PMID:Regulation of intestinal proglucagon-derived peptide secretion by intestinal regulatory peptides. 167 88

The major determinant of meal-stimulated gastric acid secretion is the antral hormone gastrin. Decarboxylated amine derivatives of amino acids have been proposed as the final common mediators of gastrin secretion stimulated by a meal. We explored the cellular basis for this hypothesis using a recently developed isolated canine G-cell model. Both amino acids and, more potently, their corresponding amines, directly stimulated gastrin release. Amino acid-stimulated gastrin secretion was unaffected by decarboxylase inhibitors (alpha methyldopa, aminooxyacetic acid, and 4-deoxypyridoxine) but enhanced by bombesin, isobutylmethylxanthine, and dibutyryl cAMP. Somatostatin inhibited amino acid-stimulated gastrin release via a pertussis toxin-sensitive GTP-binding protein. In contrast, gastrin secretion induced by amines was unaltered by any of the various treatments. Our data indicate that amino acids and amines, either as primary constituents of an ingested meal or as metabolites of dietary proteins, act directly via separate mechanisms to stimulate gastrin secretion from G-cells.
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PMID:Amino acids and amines stimulate gastrin release from canine antral G-cells via different pathways. 168 66

Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells. This peptide induced DNA synthesis in synergy with insulin in a concentration-dependent manner; half-maximum and maximum responses were achieved at 14 and 17 microM, respectively. Mastoparan also stimulated DNA synthesis in the presence of other growth promoting factors including bombesin, insulin-like growth factor-1, and platelet-derived growth factor. The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor. In contrast, mastoparan stimulated arachidonic acid release, prostaglandin E2 production, and enhanced cAMP accumulation in the presence of forskolin. These responses were inhibited by prior treatment with pertussis toxin. Hence, mastoparan stimulates arachidonic acid release via a pertussis toxin-sensitive G protein in Swiss 3T3 cells. Arachidonic acid, like mastoparan, stimulated DNA synthesis in the presence of insulin. The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment. These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis.
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PMID:Mastoparan, a novel mitogen for Swiss 3T3 cells, stimulates pertussis toxin-sensitive arachidonic acid release without inositol phosphate accumulation. 170 71

Bombesin (BB), neuromedin C (NMC) and neuromedin B (NMB) stimulated amylase secretion to similar maximum levels, with EC50 values (concentrations causing 50% of maximum effect) of 0.2, 0.3 and 2 nM respectively. Treatment of pancreatic acini with BB or NMB (10 nM) for 30 min resulted in cross-desensitization of secretory responses to subsequent BB and NMB, but not to acetylcholine, which suggests that NMB and BB activate the same receptor. BB, NMC and NMB stimulated production of similar maximum amounts of inositol mono-, bis- and tris-phosphates, with EC50 values of 3, 5 and 141 nM respectively. The bombesin receptor antagonist [Leu13-psi(CH2NH)Leu14]BB inhibited stimulation of amylase secretion and inositol phosphate formation by BB, NMC and NMB. Binding of 125I-labelled gastrin-releasing peptide (GRP; 200 pM) to rat pancreatic membranes at 22 degrees C was inhibited with relative potencies and IC50 (concn. causing 50% of maximal inhibition; nM) as follows: NMC (0.4) = BB (0.5) greater than NMB (1.8 = GRP (2.6). IC50 values for BB, NMC and NMB inhibition of 125I-GRP binding to intact acini were 5-, 19- and 68-fold higher than their respective values in membranes. The guanine nucleotide analogue guanosine 5'-[beta gamma-imido]triphosphate (Gpp[NH]p) produced rightward shifts of NMC and NMB competition curves by 3.5- and 16-fold respectively, but had little effect on the BB and GRP curves. Elevation of the temperature to 37 degrees C or inclusion of NaCl (40 mM) produced quantitatively similar effects to those of Gpp[NH]p. In the presence of both NaCl and Gpp[NH]p the affinities of peptides for membrane receptors were similar to those for intact cells. Modulation of NMB competition curves by Gpp[NH]p was not attenuated by prior treatment of acini with activated pertussis toxin. These results suggest that BB, NMB and NMC stimulate pancreatic secretion by interaction with a common phosphoinositide-linked receptor. Differences in guanine nucleotide regulation suggest that secretagogue-induced receptor-protein interactions may not be identical for NMB and BB.
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PMID:Bombesin, neuromedin B and neuromedin C interact with a common rat pancreatic phosphoinositide-coupled receptor, but are differentially regulated by guanine nucleotides. 172 Jun 12

The presence of acid in the lumen of the gastric fundus induces release of somatostatin close to the parietal cells; this acts to attenuate acid secretion in response to secretagogues, such as histamine and gastrin. The release of somatostatin within the stomach is further regulated by the activity of cholinergic neurons that inhibit somatostatin release and thus augment acid secretion (disinhibition), and noncholinergic (bombesin) neurons that stimulate somatostatin release and thus attenuate acid secretion. The influence of these neurons and the participation of somatostatin as a paracrine regulator of acid secretion has been probed and validated by the use of selective antagonists (atropine and a bombesin antagonist), somatostatin antiserum and pertussis toxin. Similar mechanisms exist in the distal antral segment of the stomach for the paracrine regulation of gastrin release by somatostatin.
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PMID:Gastric somatostatin: a paracrine regulator of acid secretion. 197 9

We recently reported that extracellular ATP was mitogenic for Swiss 3T3, 3T6, and A431 cells (Huang et al.: Proc. Natl. Acad. Sci. USA, 86:7904-7908, 1989). Here we examined the possible involvement of activation of the protein kinase C (PKC) signal transduction pathway in the mechanism of action of extracellular ATP. A potent synergistic stimulation of DNA synthesis in quiescent cultures of 3T3 and 3T6 cells was observed when ATP was presented in combination with growth factors that activate PKC, such as bombesin, vasopressin, or tumor-promoting phorbol esters. This finding suggests that ATP and these mitogens do not act through a common mechanism. In contrast, ATP was unable to show synergism with phorbol esters in A431 cells. We discovered striking differences when we examined the kinetics of formation of diacylglycerol (DAG) stimulated by ATP among these cell lines. Thus, ATP stimulated a sustained biphasic increase of DAG in A431 cells, but only a rapid transient increase of DAG formation was observed in 3T3 and 3T6 cells. The breakdown of phosphatidylcholine was stimulated by ATP in A431 cells; however, a significantly reduced effect was displayed in 3T6 cells. Furthermore, we found that the diacylglycerol-kinase inhibitor, 1-monooleoylglycerol, greatly potentiated ATP-stimulated DNA synthesis in A431 cells. Finally, down-regulation of PKC by long-term exposure to phorbol dibutyrate (PDBu) prevented stimulation of DNA synthesis induced by bombesin, vasopressin, or phorbol esters in 3T3 or 3T6 cells, while it had no such effect on ATP-stimulated mitogenesis in the presence of insulin or epidermal growth factor. On the other hand, PDBu-mediated down-regulation of PKC partially inhibited [3H [thymidine incorporation stimulated by ATP in A431 cells. Taken together, we conclude that a protein kinase C-dependent pathway is partially involved in ATP-stimulated DNA synthesis in A431 cells, but a protein kinase C-independent pathway exists in 3T3 and 3T6 cells. Pertussis toxin (PTX) inhibited the sustained phase of DAG formation and the breakdown of phosphatidylcholine stimulated by ATP in A431 cells. This suggests involvement of a PTX-sensitive G protein.
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PMID:Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells: I. Involvement of protein kinase C-dependent and -independent pathways. 202 2

We have examined the possible involvements of pertussis toxin (PT)-sensitive guanosine triphosphate (GTP)-binding protein (Gp) and protein kinase C (PKC) in the mitogenic signaling pathways of various growth factors by the use of PT-pretreated and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA)-pretreated mouse fibroblasts. Effects of PT pretreatment (inactivation of PT-sensitive Gp) and TPA pretreatment (depletion of PKC) on mitogen-induced DNA synthesis varied significantly and systematically in response to growth factors: mitogenic responses of cells to thrombin, bombesin, and bradykinin were almost completely abolished both in PT- and TPA-pretreated cells; responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vanadate were reduced to approximately 50% both in PT- and TPA-pretreated cells compared with native cells; response to basic fibroblast growth factor (bFGF) was not affected in PT-pretreated cells but was inhibited to some extent in TPA-pretreated cells. Thus, growth factors examined have been classified into three groups with regard to the involvements of PT-sensitive Gp and PKC in their signal transduction pathways. Binding of each growth factor to its receptor was not affected significantly by pretreatment of cells with PT or TPA. Inhibitory effects of PT and TPA pretreatment on each mitogen-induced DNA synthesis were not additive, suggesting that the functions of PT-sensitive Gp and PKC lie on an identical signal transduction pathway. Although all three groups of mitogens activated PKC, signaling of each growth factor depends to a varying extent on the function of PKC. Our results indicate that a single peptide growth factor such as EGF, PDGF, or bFGF acts through multiple signaling pathways to induce cell proliferation.
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PMID:Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive guanosine triphosphate-binding protein and of protein kinase C. 212 94


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