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)

Human neutrophils and HL60 cells respond to extracellular ATP by causing exocytotic secretion. Secretion is accompanied by increases in inositol phosphates and a rise in cytosol Ca2+. The responses to ATP are blocked by pertussis toxin pretreatment, indicating the involvement of a guanine nucleotide regulatory protein. Other nucleotides that are active in promoting secretion are ATP gamma S, UTP, ITP and AppNHp, whilst 8-bromo-ATP, AppCH2p, ADP, AMP and adenosine are inactive.
 ...
PMID:ATP stimulates secretion in human neutrophils and HL60 cells via a pertussis toxin-sensitive guanine nucleotide-binding protein coupled to phospholipase C. 249 77

[3H]Arachidonic acid is released after stimulation of rabbit neutrophils with fMet-Leu-Phe or platelet-activating factor (PAF). The release is rapid and dose-dependent, and is inhibited in phorbol 12-myristate 13-acetate (PMA)-treated rabbit neutrophils. The protein kinase C (PKC) inhibitor 1-(5-isoquinoline-sulphonyl)-2-methylpiperazine (H-7) prevents this inhibition. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. [3H]Arachidonic acid release, but not the rise in the concentration of intracellular Ca2+, is inhibited in pertussis-toxin-treated neutrophils stimulated with PAF. The diacylglycerol kinase inhibitor R59022 increases the concentration of diacylglycerol and potentiates [3H]arachidonic acid release in neutrophils stimulated with fMet-Leu-Phe. This potentiation is not inhibited by H-7. These results suggest several points. (1) A rise in the intracellular concentration of free Ca2+ is not sufficient for arachidonic acid release in rabbit neutrophils stimulated by physiological stimuli. (2) A functional pertussis-toxin-sensitive guanine nucleotide regulatory protein and/or one or more of the changes produced by phospholipase C activation are necessary for arachidonic acid release produced by physiological stimuli. (3) Agents that stimulate PKC potentiate arachidonic acid release, and this potentiation is not inhibited by H-7. These agents produce their actions in part by direct membrane perturbation.
 ...
PMID:Arachidonic acid release in rabbit neutrophils. 277 41

Brief exposure of hepatocytes to glucagon, angiotensin or the protein kinase C activator TPA (12-O-tetradecanoylphorbol 13-acetate) caused the inactivation of the inhibitory guanine nucleotide regulatory protein Gi. Glucagon-mediated desensitization of glucagon-stimulated adenylate cyclase activity was seen in hepatocytes from both normal rats and those made diabetic with streptozotocin, where Gi is not functionally expressed. Normal glucagon desensitization was seen in hepatocytes from young animals, 6 weeks of age, which had amounts of Gi in their hepatocyte membranes which were some 45% of that seen in mature animals (3.4 pmol/mg of plasma-membrane protein). Streptozotocin-induced diabetes in young animals abolished the appearance of functional Gi in hepatocyte plasma membranes. Pertussis-toxin treatment of hepatocytes from both normal mature animals and those made diabetic, with streptozotocin, blocked the ability of glucagon or angiotensin or TPA to elicit desensitization of adenylate cyclase. The isolated B (binding)-subunit of pertussis toxin was ineffective in blocking desensitization. Neither induction of diabetes nor treatment of hepatocytes with pertussis toxin inhibited the ability of glucagon and angiotensin to stimulate the production of inositol phosphates in intact hepatocytes. Thus (i) Gi does not appear to play a role in the molecular mechanism of glucagon desensitization in hepatocytes, (ii) the G-protein concerned with receptor-stimulated inositol phospholipid metabolism in hepatocytes appears not to be a substrate for the action of pertussis toxin, (iii) in intact hepatocytes, treatment with glucagon and/or angiotensin can elicit the inactivation of the inhibitory G-protein Gi, and (iv) pertussis toxin blocks desensitization by a process which does not involve Gi.
 ...
PMID:Glucagon desensitization of adenylate cyclase and stimulation of inositol phospholipid metabolism does not involve the inhibitory guanine nucleotide regulatory protein Gi, which is inactivated upon challenge of hepatocytes with glucagon. 249 30

Transforming growth factor beta (TGF beta 1) is a potent regulator of DNA synthesis and cellular proliferation. In this study, we investigated whether the growth stimulatory signal of TGF beta 1 is transduced intracellularly by guanine nucleotide regulatory proteins (G-proteins). In plasma membranes from AKR-2B cells, TGF beta 1 increased binding of the radiolabelled, non-hydrolysable GTP analogue, guanosine 5'-[gamma-[35S]thio]triphosphate (GTP[35S]), in a dose-dependent manner. Maximal effects occurred between 0.4 and 1.0 nM-TGF beta 1. Specific binding of GTP[35S] occurred with a Kd of 3.2 x 10(-8) M which was not affected by addition of TGF beta 1. Instead, TGF beta 1 increased the number of available binding sites for GTP[35S] from 16.2 +/- 1.2 to 21.6 +/- 2.1 pmol/mg of protein. GTP[35S] binding was both nucleotide- and growth-factor-specific. Only guanine nucleotides were able to compete for binding, and of the growth factors tested (epidermal growth factor, platelet-derived growth factor, insulin, TGF beta 1 and TGF beta 2) only TGF beta 1 affected GTP[35S] binding. TGF beta 1 increased GTPase activity, as determined by the release of 32PO4(3-) from GTP gamma[32P], from 116 +/- 5.5 to 175 +/- 4.3 pmol/mg of protein following a 15 min incubation. Pretreatment of the membranes with pertussis toxin inhibited both TGF beta 1-stimulated binding of GTP[35S] as well as TGF beta 1-stimulated GTPase activity. These inhibitory actions of pertussis toxin were associated with toxin-induced ADP-ribosylation of a 41 kDa protein. Furthermore, the stimulatory effects of TGF beta 1 on c-sis mRNA expression were shown to be pertussis-toxin sensitive and could be mimicked by direct activation of G-proteins with AIF4-. These results demonstrate that in AKR-2B cells a pertussis-toxin-sensitive guanine nucleotide regulatory protein(s) is coupled to TGF beta 1 receptor binding.
 ...
PMID:Transforming growth factor beta 1 treatment of AKR-2B cells is coupled through a pertussis-toxin-sensitive G-protein(s). 250 23

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; PAF) enhances the release of newly synthesized PAF as measured by [3H]acetate incorporation into PAF in human neutrophils. The response was dose-dependent, rapid, transient, and inhibitable by the PAF antagonist BN-52021. The non-metabolizable bioactive PAF analogue (C-PAF) but not lyso-PAF enhances the release of newly synthesized PAF. Newly synthesized PAF was also released after stimulation of these cells with fMet-Leu-Phe. The human granulocyte-macrophage colony-stimulating factor potentiates the stimulated release of PAF. The intracellular calcium chelator BAPTA inhibits the rise of [Ca2+]i and the release of PAF but not the Na+/H+ antiport activity. PAF release, but not the rise in the intracellular concentration of free calcium, was inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The release of PAF in pertussis toxin-treated cells was also inhibited in cells stimulated with fMet-Leu-Phe or opsonized zymosan. These results suggest that functional pertussis toxin-sensitive guanine nucleotide regulatory protein and/or one or more of the changes produced by phospholipase C activation are necessary for PAF release produced by physiological stimuli. It appears that PAF release requires a coordinated action of receptor-coupled G-proteins, calcium, and other parameters.
 ...
PMID:Calcium is necessary but not sufficient for the platelet-activating factor release in human neutrophils stimulated by physiological stimuli. Role of G-proteins. 251 17

Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release.
 ...
PMID:Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator. 253 15

We have examined the regulation by prostaglandin E2 (PGE2) of hormone-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cells isolated by immunodissection from both the medullary and cortical thick ascending limb of Henle's loop of rabbit kidney. At concentrations greater than 10(-8) M, PGE2, but not sulprostone (16-phenoxy-17,18,19,20-tetranor-PGE2 methylsulfonilamide), caused cAMP accumulation in both cortical and medullary thick limb cells. However, at concentrations of less than or equal to 10(-8) M, both PGE2 and sulprostone inhibited arginine vasopressin (AVP)-, calcitonin-, and glucagon-induced cAMP accumulation in medullary thick ascending limb (mTAL) cells. In cortical thick limb (cTAL) cells, sulprostone also inhibited AVP-, calcitonin-, and parathyroid hormone (PTH)-induced cAMP accumulation. The inhibitory effects of PGE2 and of sulprostone were blocked by pretreatment of mTAL and cTAL cells with pertussis toxin. Membranes prepared from mTAL cells exhibited a [3H]PGE2 binding activity that was stimulated on addition of the stable guanosine 5'-triphosphate (GTP) analogue, 5'-guanosine gamma-thiotriphosphate (GTP gamma S); moreover, sulprostone inhibited [3H]PGE2 binding. Our results suggest that PGE2 can function via a prostaglandin E receptor linked to a guanine nucleotide regulatory protein, Gi, to attenuate hormone-induced cAMP formation in both mTAL and cTAL cells of rabbit kidney.
 ...
PMID:Regulation of cAMP metabolism by PGE2 in cortical and medullary thick ascending limb of Henle's loop. 253 67

Neuropeptide Y (NPY) regulation of intracellular cyclic AMP accumulation was studied in human Ewing's sarcoma cell line, WE-68. NPY inhibited vasoactive intestinal peptide (VIP)- and dopamine-stimulated but not basal cyclic AMP formation. The peptide effect was rapid (less than 2 min), concentration-dependent with a half-maximal effective concentration (EC50) of 8 nM NPY, and maximal inhibition reaching 60-70% with 100 nM NPY. Prior exposure of WE-68 cells to pertussis toxin completely abolished the inhibitory action of NPY. It is concluded that NPY attenuates agonist-stimulated cyclic AMP formation in Ewing's sarcoma WE-68 cells, and may do so via the inhibitory guanine nucleotide regulatory protein of adenylate cyclase.
 ...
PMID:Neuropeptide Y inhibits vasoactive intestinal peptide- and dopamine-induced cyclic AMP formation in human Ewing's sarcoma WE-68 cells. 254 51

We have recently shown that F- can mimic the actions of cholecystokinin (CCK) on amylase release, Ca2+ mobilization and inositol phosphate generation in pancreatic acinar cells. We have concluded, therefore, that pancreatic CCK receptors may be coupled to the activation of polyphosphoinositide hydrolysis by a guanine nucleotide regulatory protein (N protein), which seems to be sensitive to F-. In the present study, in order to further characterize this N protein coupled to pancreatic CCK receptors, we have examined the effects of bacterial toxins, pertussis toxin (PT) and cholera toxin (CT) on both CCK- and NaF-induced cellular responses in isolated rat pancreatic acini. Neither PT or CT pretreatment of acini affected both CCK- and NaF-stimulated increases in intracellular Ca2+ concentration monitored by quin2. Furthermore, pretreatments of acini with PT and CT didn't alter the effects of CCK on inositol phosphate generation in acini. Similarly, NaF-induced inositol phosphate generation was not changed by these toxin treatments. However, pretreatment procedures employed in this study were considered to catalyze complete ADP-ribosylation of alpha-subunit of the stimulatory (Ns) and inhibitory (Ni) N protein. These results, therefore, strongly suggest that a N protein coupling pancreatic CCK receptors to the breakdown of polyphosphoinositide may be distinct from Ns or Ni like protein.
 ...
PMID:[Role of a guanine nucleotide regulatory protein in exocrine pancreatic secretion--effects of cholera toxin and pertussis toxin on cholecystokinin action]. 255 6

Bradykinin inhibits vasopressin-stimulated water transport in cortical collecting tubular cells. The biochemical mechanism of this effect was explored by means of primary cultures of rabbit cortical collecting tubular cells. Bradykinin was found to produce a rapid release of calcium from intracellular stores, an increase in sn-1,2-diacylglycerol levels, and a fivefold increase in membrane-bound protein kinase C activity, consistent with stimulation of phospholipase C and activation of protein kinase C in rabbit cortical collecting tubular cells. In addition, bradykinin produced a dose-dependent 46% inhibition of vasopressin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. Pretreatment with the protein kinase C inhibitors, H-7 and staurosporine, reversed the bradykinin-mediated inhibition of vasopressin-stimulated cAMP accumulation. In contrast, pretreatment with either the phospholipase A2 inhibitor, mepacrine, or pertussis toxin did not prevent the inhibitory effect of bradykinin on vasopressin-stimulated cAMP production, suggesting that the effects are not mediated by prostaglandin E2 or activation of a pertussis-toxin sensitive guanine nucleotide regulatory protein (e.g., Gi). Because bradykinin also inhibits isoproterenol-stimulated cAMP formation but does not inhibit either basal-, forskolin-, or cholera toxin-stimulated cAMP accumulation, the site of this inhibition appears to involve the hormone receptor or coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit (Gs). The results demonstrate that bradykinin stimulates phospholipase C leading to activation of protein kinase C, which then inhibits vasopressin-stimulated cAMP production at the level of the hormone receptor or coupling of the receptor to Gs in cultured cortical collecting tubular cells.
 ...
PMID:Bradykinin activates protein kinase C in cultured cortical collecting tubular cells. 255 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>