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

The direct inhibition of secretion by pancreastatin was investigated in rabbit isolated parietal cells. Pancreastatin exerted no influence on basal aminopyrine uptake. Pancreastatin inhibited histamine stimulated aminopyrine uptake through a decrease in intracellular cAMP. Pancreastatin inhibition of histamine stimulated uptake was blocked in the presence of pertussis toxin. Pancreastatin also inhibited the carbachol stimulated increase in aminopyrine accumulation. However, the effects of pancreastatin on carbachol stimulation were not reversed by pertussis toxin. Pancreastatin did not alter the carbachol induced increase in cytosolic free calcium. Thus, pancreastatin appears to inhibit parietal cell signal transduction at multiple points along the second messenger pathways.
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PMID:Pancreastatin: a novel peptide inhibitor of parietal cell signal transduction. 255 Dec 71

Pancreastatin inhibited carbachol- but not forskolin- or GIP-stimulated insulin release from Rin m 5F cells. The inhibition induced by pancreastatin was dose-dependent, with an ED50 value of 4 nM, and reached a maximum (50% of inhibition) at 10(-7) M peptide. Pretreatment of cells with pertussis toxin abolished the inhibitory effect of pancreastatin on carbachol-induced insulin release. We suggest that pancreastatin exerts a direct inhibitory control on insulin release through a pertussis toxin-sensitive cAMP-independent pathway.
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PMID:Pancreastatin inhibits insulin release from Rin m 5F cells: reversion by pertussis toxin. 265 48

We have recently found the calcium dependent glycogenolytic effect of a pancreastatin on rat hepatocytes and the mobilization of intracellular calcium. To further investigate the mechanism of action of pancreastatin on liver we have studied its effect on guanylate cyclase, adenylate cyclase, and phospholipase C, and we have explored the possible involvement of GTP binding proteins by measuring GTPase activity as well as the effect of pertussis toxin treatment of plasma liver membranes on the pancreastatin stimulated GTPase activity and the production of cyclic GMP and myo-inositol 1,4,5-triphosphate. Pancreastatin stimulated GTPase activity of rat liver membranes about 25% over basal. The concentration dependency curve showed that maximal stimulation was achieved at 10(-7)M pancreastatin (EC50 = 3 nM). This stimulation was partially inhibited by treatment of the membranes with pertussis toxin. The effect of pancreastatin on guanylate cyclase and phospholipase C were examined by measuring the production of cyclic GMP and myo-inositol 1,4,5-triphosphate respectively. Pancreastatin increased the basal activity of guanylate cyclase to a maximum of 2.5-fold the unstimulated activity at 30 degrees C, in a time- and dose-dependent manner, reaching the maximal stimulation above control with 10(-7) M pancreastatin at 10 min (EC50 = 0.6 nM). This effect was completely abolished when rat liver membranes had been ADP-ribosylated with pertussis toxin. On the other hand, adenylate cyclase activity was not affected by pancreastatin. Phospholipase C activity of rat liver membranes was rapidly stimulated (within 2-5 min) at 30 degrees C by 10(-7) M pancreastatin, reaching a maximum at 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pancreastatin activates pertussis toxin-sensitive guanylate cyclase and pertussis toxin-insensitive phospholipase C in rat liver membranes. 791 48

Pancreastatin is a 49 amino acid peptide first isolated, purified and characterized from porcine pancreas. Its biological activity in different tissues can be assigned to the C-terminal part of the molecule. Pancreastatin has a prohormonal precursor, chromogranin A, which is a glycoprotein present in neuroendocrine cells, including the endocrine pancreas. We have been interested in pancreastatin action in the liver. We found that pancreastatin has a glycogenolytic effect in the hepatocyte both in vivo and in vitro. We then studied and characterized the specific pancreastatin receptor in the rat liver plasma membrane, as well as the specific signal transduction. This receptor appears to be coupled to two different G proteins. A pertussis toxin-insensitive G proteins leads to the activation of phospholipase C, and therefore mediates the glycogenolytic effect in the liver by increasing cytoplasmic free calcium and stimulating protein kinase C. The role of cyclic GMP in the action of pancreastatin is not known yet, although it seems to regulate negatively the activation of phospholipase C. The precise mechanism by which pancreastatin stimulates guanylate cyclase activity remains to be studied.
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PMID:Pancreastatin action in the liver: dual coupling to different G proteins. 877 44

Pancreastatin (PST), a recently discovered regulatory peptide derived from chromogranin A, has been shown to have a glycogenolytic effect in the hepatocyte that is mediated by increasing intracellular calcium. Our previous studies on pancreastatin signaling suggested that PST receptor is coupled to some G proteins in the plasma membrane of the hepatocyte. The nature of this interaction was investigated using antisera against G(q/11)alpha by different approaches. Indirect evidence of a pertussis toxin (PT)-insensitive G protein of the family of G(q/11)alpha was obtained by measuring high-affinity guanosine triphosphatase (GTPase) activity in soluble rat liver membranes. PST increased GTPase activity in a dose-dependent manner. This effect was only slightly inhibited by PT pretreatment of the membranes, whereas anti-G(q/11)alpha antisera blocked most of the PST-stimulated GTPase activity. The selective association of the PST receptor with this G protein was further studied by the coelution in wheat germ agglutinin semipurification of the receptor and by immunoprecipitation of the G protein-PST receptor complexes using G-protein-specific antisera. A G protein of the family of G(q/11)alpha was found to be associated with the semipurified PST receptor. Moreover, anti-G(q/11)alpha antisera immunoprecipitated most PST-binding activity (95%), bringing down most of the specific G protein, whereas anti-G(il,2)alpha and -G(o,i3)alpha failed to immunoprecipitate the PST-binding activity. Finally, the coupling of the PST receptor with the effector phospholipase C was disrupted by blocking with G(q/11)alpha antisera, suggesting that a G protein of the family of G(q/11)alpha is a signal mediator from PST receptors to phospholipase C activation in rat liver membranes.
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PMID:Pancreastatin receptor is coupled to a guanosine triphosphate-binding protein of the G(q/11)alpha family in rat liver membranes. 946 64

Pancreastatin (PST) receptors have been recently shown to mediate activation of phospholipase C (PLC) in rat liver membranes. There is evidence that the G protein that links pancreastatin receptor with PLC-beta is pertussis toxin-insensitive and belongs to the G(alpha)q family. Here, we have employed blocking antisera to sort out the specific PLC-beta isoform as well as the specific G(alpha) subunit activated by PST receptor in rat liver membranes. The presence of different PLC-beta isoforms was checked by immunoblot analysis. Only PLC-beta4 was not detected, whereas PLC-beta1, beta2 and beta3 were abundant in rat liver membranes. However, only anti-PLC-beta3 serum was able to block the PST receptor response. We also checked the expression of G(alpha)q and Galpha11 in rat liver membranes by immunoblot. Even though both isoforms were present. only anti-Galpha11 serum was able to block the PST receptor response. In order to check the specificity of the blocking antisera, we employed them to block the effect of ADP and thrombin stimulating PLC activity in platelet membranes, a system lacking Galpha11. Anti-G(alpha)q but not anti-Galpha11 sera were able to block the agonist stimulated PLC activity. These data suggest that PST receptor response is mediated by the activation of the beta3 isoform of PLC via Galpha11 protein stimulation in rat liver membranes.
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PMID:Pancreastatin activates beta3 isoform of phospholipase C via G(alpha)11 protein stimulation in rat liver membranes. 980 54

Pancreastatin (PST), a chromogranin A derived peptide with an array of effects in different tissues, has a role as a counterregulatory hormone of insulin action in hepatocytes and adipocytes, regulating glucose, lipid and protein metabolism. We have previously characterized PST receptors and signaling in rat hepatocytes, in which PST functions as a calcium-mobilizing hormone. In the present work we have studied PST receptors as well as the signal transduction pathways generated upon PST binding in adipocyte membranes. First, we have characterized PST receptors using radiolabeled PST as a ligand. Analysis of binding data indicated the existence of one class of binding sites, with a B(max) of 5 fmol/mg of protein and a K(d) of 1 nM. In addition, we have studied the G protein system that couples the PST receptor by gamma-(35)S-GTP binding studies. We have found that two G protein systems are involved, pertussis toxin-sensitive and -insensitive respectively. Specific anti-G protein alpha subtype sera were used to block the effect of pancreastatin receptor activation. Galpha(q/11) and to a lesser extent Galpha(i1,2) are activated by PST in rat adipocyte membranes. On the other hand, adenylate cyclase activity was not affected by PST. Finally, we have studied the specific phospholipase C isoform that is activated in response to PST. We have found that PST receptor is coupled to PLC-beta(3) via Galpha(q/11) activation in adipocyte membranes.
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PMID:Characterization of pancreastatin receptors and signaling in adipocyte membranes. 1044 97

In the liver, pancreastatin exerts a glycogenolytic effect through interaction with specific receptors, followed by activation of phospholipase C and guanylate cyclase. Pancreastatin receptor seems to be coupled to two different G protein systems: a pertussis toxin-insensitive G protein that mediates activation of phospholipase C, and a pertussis toxin sensitive G protein that mediates the cyclic GMP production. The aim of this study was to identify the specific G protein subtypes coupling pancreastatin receptors in rat liver membranes. GTP binding was determined by using gamma-35S-GTP; specific anti-G protein alpha subtype sera were used to block the effect of pancreastatin receptor activation. Activation of G proteins was demonstrated by the incorporation of the photoreactive GTP analogue 8-azido-alpha-32P-GTP into liver membranes and into specific immunoprecipitates of different Galpha subunits from soluble rat liver membranes. Pancreastatin stimulation of rat liver membranes increases the binding of gamma-35S-GTP in a time- and dose-dependent manner. Activation of the soluble receptors still led to the pancreastatin dose-dependent stimulation of gamma-35S-GTP binding. Besides, WGA semipurified receptors also stimulates GTP binding. The binding was inhibited by treatment with anti-Galphaq/11 (85%) and anti-Galphai1,2 (15%) sera, whereas anti-Galphao,i3 serum failed to affect the binding. Finally, pancreastatin stimulates GTP photolabeling of particulate membranes. Moreover, it specifically increased the incorporation of 8-azido-alpha-32P-GTP into Galphaq/11 and Galpha, but not into Galphao,i3 from soluble rat liver membranes. In conclusion, pancreastatin stimulation of rat liver membranes led to the activation of Galphaq/11 and Galphai1,2 proteins. These results suggest that Galphaq/11 and Galphai1,2 may play a functional role in the signaling of pancreastatin receptor by mediating the production of IP3 and cGMP respectively.
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PMID:G protein G alpha q/11 and G alpha i1,2 are activated by pancreastatin receptors in rat liver: studies with GTP-gamma 35S and azido-GTP-alpha-32P. 1073 41

Pancreastatin, a chromogranin A derived peptide, exerts a glycogenolytic effect on the hepatocyte. This effect is initiated by binding to membrane receptors which are coupled to pertussis toxin insensitive G proteins belonging to the Gq/11 family. We have recently solubilized active pancreastatin receptors from rat liver membranes still functionally coupled to G proteins. Here, we have purified pancreastatin receptors by a two-step procedure. First, pancreastatin receptors with their associated Gq/11 regulatory proteins were purified from liver membranes by lectin absorption chromatography on wheat germ agglutinin immobilized on agarose. A biotinylated rat pancreastatin analog was tested for binding to liver membranes before using it for affinity purification. Unlabeled biotinylated rat pancreastatin competed for 125I-labeled [Tyr0]PST binding to solubilized receptors with a Kd = 0.27 nM, comparable to that of native pancreastatin. The biotinylated analog was immobilized on streptavidin-coated Sepharose beads and used to further affinity purify wheat germ agglutinin eluted receptor material. Specific elution at low pH showed that the receptor protein was purified as an 80-kDa protein in association with a G protein of the q/11 family, as demonstrated by specific immunoblot analysis. The specificity of the receptor band was assessed by chemical cross-linking of the purified material followed by SDS-PAGE and autoradiography. In conclusion, we have purified pancreastatin receptor as a glycoprotein of 80 kDa physically associated with a Gq/11 protein.
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PMID:Affinity purification of pancreastatin receptor-Gq/11 protein complex from rat liver membranes. 1087 Oct 55

N-terminal peptides of chromogranin A and B (CGA and CGB) were compared for dilator responses in isolated bovine coronary arteries (bCoA), measuring diameter changes as a function of pressure. bCoA developed and maintained myogenic tone (MYT) at approximately 20% from 50 to 150 mm Hg. In contrast to CGB(1-40), CGA(1-40) and CGA(1-76) (VS-I) both displayed significant intrinsic vasodilator effects. CGA(1-40) reduced myogenic reactivity from 70 to 150 mm Hg (p<0.05, n=6). At 75 mm Hg, CGA(1-40) showed a concentration-dependent dilatation at 0.1 nM-10 microM. The dilator effect of CGA(1-40) persisted at moderately elevated [K(+)](e) (8.4-16 mM). However, this effect was diminished by pertussis toxin (PTX) and abolished by antagonists to several subtypes of K(+) channels (tetraethylammonium, Ba(2+) and glibenclamide). These results demonstrate that the N-terminal domain of CGA has dilator effect in the myogenically active bCoA. We propose that CGA(1-40) and the naturally occurring vasostatin I are regulatory peptides of relevance for the coronary microcirculation and that a G(alphai) sub-unit and K(+) channel activation may be involved in the signal pathway.
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PMID:N-terminal chromogranin-derived peptides as dilators of bovine coronary resistance arteries. 1189 Oct 9


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