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)

1. In order to determine the intracellular mechanisms by which galanin induces contraction of isolated smooth muscle cells from pig ileum, we examined the effects of external Ca2+, relaxing agents, pertussis toxin and forskolin on the galanin-induced contraction and compared these effects to those observed on the cholecystokinin derivative CCK8-induced contraction. 2. Galanin induced a concentration-dependent cell contraction. The maximal contraction (24.5 +/- 2.1% of the length of resting cells) was observed at 1 nM of galanin. When cells were incubated in the simultaneous presence of concentrations of galanin (10 fM) and CCK8 (1 pM) which were ineffective alone, or galanin (10 fM) and acetylcholine (100 pM), a synergistic action was observed corresponding to a submaximal contraction. 3. Incubation of cells in Ca(2+)-free medium caused a significant decrease in galanin- but not in CCK-induced contraction. Nifedipine, a Ca2+ channel blocker, provoked a concentration-dependent inhibition of galanin-induced contraction while it had no effect on the contraction induced by CCK8. 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin. 5. When cells were pre-incubated for 3 h in the presence of 200 ng/ml of pertussis toxin, the contraction induced by galanin was abolished while the CCK-induced contraction remained unchanged. On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction. 6. These results indicate that galanin induces a concentration-dependent contraction of pig ileum smooth muscle by a direct myogenic effect. This effect of galanin involves the activation of a pertussis toxin-sensitive G protein, which results in an influx of Ca2+ into the cell. This intracellular pathway is insensitive to the relaxing effect of cAMP.
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PMID:Intracellular pathways triggered by galanin to induce contraction of pig ileum smooth muscle cells. 128 68

The regulated secretory pathway comprises accelerated discharge of proteins in response to hormonal stimuli, their presence in secretory granules (SG), and a long intracellular residence time. Dexamethasone induction of AR42J results in an increase in granule content and responsiveness to cholecystokinin (CCK). We studied the effects of conditions implicated in sorting of secretory proteins into the regulated pathway using [35S]methionine pulse-chase protocols that examine transport of secretory proteins from the rough endoplasmic reticulum (RER)----SG and specifically from the Golgi complex (GC)----SG. The latter uses a chase at 20 degrees C to allow accumulation of labeled proteins in the trans-Golgi, followed by a shift to 37 degrees C that initiates their transport to SG under test conditions. Quantitation of CCK-8-stimulated discharge of prestored amylase and of newly synthesized labeled proteins that have entered SG during the chase enables us to examine the effect of perturbants over selected parts of the pathway. The effects of acidic intracellular compartments, the cytoskeleton, protein synthesis, ATP, and temperature on pre- and post-Golgi entry of proteins into the regulated pathway were studied. NH4Cl, monensin, Na azide, incubation at 20 degrees C, and pertussis toxin retarded RER----SG transport without affecting amylase discharge. Only incubation with 20 mM NH4Cl or 1 microM monensin inhibited transfer of newly synthesized proteins from the late GC----SG. RER----Golgi or intra-Golgi transport thus appears to require ATP and possibly guanosine 5'-triphosphate (GTP)-binding proteins. Acidic compartments appear to be essential for sorting of secretory proteins from the GC----SG.
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PMID:Perturbation of regulated secretion in the pancreatic acinar cell line, AR42J. 137 45

Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.
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PMID:Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach. 164 73

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

In rat pancreatic acinar cells epidermal growth factor (EGF) and insulin increase both basal and cholecystokinin (CCK-OP) stimulated amylase release in vitro (1) as a long term function of this tissue. Here we show that preincubation of isolated plasma membranes with EGF or with insulin leads to increased incorporation of the GTP-photoaffinity analogue [alpha-32P]GTP-gamma-azidoanilide into 40/41 kDa proteins and to reduction of pertussis toxin- (PT) catalyzed [alpha-32P]ADP-ribosylation of three 40/41 kDa proteins which had been previously identified as Gi1, Gi2 and Gi3 (2). In the presence of GTP gamma S, EGF- and insulin-induced inhibition of PT-mediated [alpha-32P]ADP-ribosylation of 40/41 kDa proteins is eliminated. EGF enhances cholera toxin- (CT) mediated ADP-ribosylation of all three 40/41 kDa Gi-proteins as well as of five 45 and four 48/50 kDa proteins, which had been previously identified as Gs-proteins (2), whereas insulin has no effect. We conclude from our data that both EGF and insulin interact with the same Gi-proteins as CCK-OP does, whereas EGF additionally interacts with nine Gs-proteins. It is likely that one, two or all three 40/41 kDa Gi-proteins are involved in insulin- and EGF-induced potentiation of CCK-OP-stimulated enzyme secretion. In addition interaction of EGF with Gs-protein could play a role in the potentiation of CCK-OP-induced enzyme secretion from pancreatic acinar cells.
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PMID:Receptors for insulin interact with Gi-proteins and for epidermal growth factor with Gi- and Gs-proteins in rat pancreatic acinar cells. 190 90

Neuropeptide Y (NPY) is a unique peptide with wide distribution in central and peripheral nervous systems. In the guinea pig, NPY-positive fibers are prominent in the myenteric plexus. To test whether NPY inhibits myenteric plexus acetylcholine (ACh) release and to define mechanisms, a purified preparation of myenteric plexus neurons was derived from the teniae coli of neonatal guinea pigs and maintained in primary culture. Incubation of cultured neurons labeled with [3H]ACh in the presence of NPY (10(-14)-10(-6) M) significantly inhibited basal ACh release (83 +/- 16 to 58 +/- 11% of control). NPY significantly inhibited ACh release stimulated by potassium (55 mM); by adenylate cyclase agonists forskolin (10(-6) M) and cholera toxin (10(-8) M); and by calcitonin gene-related peptide, cholecystokinin octapeptide, and vasoactive intestinal peptide (each 10(-8) M). In each instance, the inhibitory effects of NPY were reversed by preincubation with pertussis toxin. Reversal of inhibitory effects by pertussis toxin suggests that the actions of NPY are mediated via an inhibitory GTP-binding protein.
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PMID:Inhibition of acetylcholine release from guinea pig myenteric neurons by neuropeptide Y: GTP-binding protein mediation. 190 63

On separation of rat pancreatic plasma membrane proteins by two-dimensional gel electrophoresis, 15 GTP-binding protein (G-protein) alpha-subunits could be detected immunochemically using an alpha common antibody. These consisted of five 48 kDa proteins (pI 5.70, 5.80, 5.90, 6.10 and 6.25) and five 45 kDa proteins (pI 5.90, 6.05, 6.25, 6.30 and 6.70), presumably corresponding to low- and high-molecular mass forms of the Gs-protein, as well as three 40/41 kDa proteins (pI 5.50, 5.70 and 6.00) and two 39 kDa proteins (pI 5.50 and 6.00). All of these proteins except for the more acidic 39 kDa protein were ADP-ribosylated by cholera toxin (CT). In addition, the three 40/41 kDa proteins and the more alkaline 39 kDa protein were also ADP-ribosylated by pertussis toxin (PT). CT- and PT-induced ADP-ribosylation changed the pI values of G-protein alpha-subunits by 0.2 pI units to more acidic values. Preincubation of isolated pancreatic membranes with cholecystokinin octapeptide (CCK-OP), which stimulates phospholipase C in acinar cells, decreased CT-induced as well as PT-induced ADP-ribosylation of the three 40/41 kDa proteins, whereas CT-induced ADP-ribosylation of one 45 kDa (pI 5.80) and all 48 kDa proteins was enhanced in the presence of CCK. Carbachol, another stimulant of phospholipase C, had no effect. The three 40/41 kDa proteins and one 48 kDa protein could be labelled with the GTP analogue [alpha-32P]GTP-gamma-azidoanilide. CCK, but not carbachol, stimulated incorporation of the GTP analogue into all of these four proteins. Using different anti-peptide antisera specific for alpha-subunits of G-proteins we identified the three 40/41 kDa Gi-proteins as Gi1 (pI 6.00), Gi2 (pI 5.50) and Gi3 (pI 5.70). The Gi3-protein was found to be the major Gi-protein of pancreatic plasma membranes. One of the 39 kDa proteins (pI 6.0) was identified as Go. These results indicate that CCK receptors functionally interact with six Gs-proteins and with Gi1, Gi2 and Gi3-proteins. Since evidence suggests that a 40/41 kDa CT substrate is involved in the stimulation of phospholipase C in pancreatic acinar cells, it is likely that one, two or all three 40/41 kDa Gi-proteins are involved in the coupling of CCK receptors with phospholipase C.
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PMID:Cholecystokinin activates Gi1-, Gi2-, Gi3- and several Gs-proteins in rat pancreatic acinar cells. 211 41

In isolated guinea pig gastric chief cells, sodium fluoride (NaF) stimulated a monophasic increase in diacylglycerol accumulation, while cholecystokinin (CCK) strongly stimulated its biphasic accumulation. NaF evoked an increase in initial Ca2+ influx rate with a slow increase in intracellular free Ca2+ concentration [( Ca2+]i), while CCK stimulated a rapid increase in [Ca2+]i followed by a late sustained phase of the [Ca2+]i increase. Lanthanum chloride (La3+) effectively blocked NaF-stimulated increase in [Ca2+]i, but it blocked only CCK-stimulated late sustained phase of [Ca2+]i increase. The effect of NaF on pepsinogen secretion was enhanced in the presence of 100 microM AlCl3. Furthermore, pertussis toxin did not affect NaF-evoked diacylglycerol accumulation at all. These results suggest that NaF may activate a pertussis-toxin insensitive guanine nucleotide regulatory protein (G protein) coupled to a signal transducing mechanism which seems to be distinct from that activated by CCK, thereby inducing increases in diacylglycerol accumulation, Ca2+ influx and pepsinogen secretion in guinea pig gastric chief cells.
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PMID:Difference in effects of sodium fluoride and cholecystokinin on diacylglycerol accumulation and calcium increase in guinea pig gastric chief cells. 240 88

The role of a pertussis toxin sensitive GTP-binding protein in mediating between cholecystokinin receptors and phosphatidylinositol 4,5-bisphosphate phosphodiesterase as well as in preventing cholecystokinin from increasing cellular cyclic AMP has been investigated using dispersed acini from rabbit pancreas. Pertussis toxin pretreatment (500 ng/ml, 2 h) did not affect cholecystokinin(octapeptide) (CCK-8)-induced increases in cytosolic free Ca2+ as judged from changes in fluorescence obtained from quin2-loaded acini. Although pretreatment with pertussis toxin was also without effect on resting acinar cell cyclic AMP levels, adenylate cyclase activity was increased, since inhibition of cyclic AMP phosphodiesterase activity by isobutylmethylxanthine (IBMX) resulted in an additional increase in cyclic AMP levels in toxin-treated acini, indicating that acinar cell adenylate cyclase activity is under some tonic inhibitory control by the pertussis toxin-sensitive inhibitory GTP-binding protein (Gi) of the adenylate cyclase system. CCK-8 gave an increase in cyclic AMP levels in both control (1.6-fold) and toxin-treated (2.3-fold) acini, leading to cyclic AMP levels in the toxin-treated acini 2-times as high as those in control acini. In the presence of IBMX, the cyclic AMP response to CCK-8 was again markedly enhanced in acini pretreated with the toxin (3.2- vs. 1.8-fold), resulting in cAMP levels in the toxin-treated acini 3.7-times those in the absence of IBMX, 2.5-times those in control acini in the presence of IBMX and 7.0-times those in control acini in the absence of IBMX. Neither the pretreatment with pertussis toxin, nor the presence of IBMX alone, nor the combination had an effect on basal amylase secretion. However, all three treatments potentiated the stimulatory effect of CCK-8 on amylase secretion and the amount of potentiation was proportional to the cyclic AMP levels reached. Our findings suggest that in the intact pancreatic acinar cell Gi inhibition of the catalytic subunit of the adenylate cyclase may largely be responsible for preventing cholecystokinin from increasing cellular cyclic AMP. They moreover show that cyclic AMP is a modulatory agent in rabbit pancreatic enzyme secretion, not able to stimulate secretion itself, but potentiating effects mediated by the phosphatidylinositol-calcium pathway.
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PMID:Pertussis toxin stimulates cholecystokinin-induced cyclic AMP formation but is without effect on secretagogue-induced calcium mobilization in exocrine pancreas. 243 69

The two mammalian neuropeptides substance P (SP) and neurokinin A (NKA) have been demonstrated to stimulate DNA synthesis in connective tissue cells, suggesting that peripheral neurons may play a role in development and tissue regeneration. In this study we have tried to identify intracellular messengers required for SP- and NKA-induced DNA synthesis. SP and NKA, as well as platelet-derived growth factor (PDGF) stimulated formation of inositol phosphates in smooth muscle cells (SMC), whereas no effect on inositol phosphates formation occurred in response to nonmitogenic neuropeptides. Pretreatment of the cells with pertussis toxin markedly decreased DNA synthesis induced by NKA. This toxin inhibits formation of inositol phosphates by acting on a regulatory G-protein. Calcium and calmodulin antagonists also inhibited NKA-induced DNA synthesis. These results imply that the mitogenic signal(s) produced by activated neuropeptide receptors involves formation of inositol phosphate and activation of a calcium/calmodulin dependent process. We further report that other neuropeptides occurring in peripheral neurons, i.e., vasoactive intestinal polypeptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, or cholecystokinin, are without growth-stimulatory effect on cultured SMC.
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PMID:Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A. 245 38


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