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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G proteins act as transducers between membrane receptors activated by extracellular signals and enzymatic effectors controlling the concentration of cytosolic signal molecules such as cAMP, cGMP, inositol phosphates and Ca2+. In some instances, the receptor/G protein-induced changes in the concentration of cytosolic signal molecules correlate with activity changes of voltage-dependent Ca2+ channels. Ca2+ channel modulation, in these cases, requires the participation of protein kinases whose activity is stimulated by cytosolic signal molecules. The respective protein kinases phosphorylate Ca2+ channel-forming proteins or unknown regulatory components. More recent findings suggest another membrane-confined mechanism that does not involve cytosolic signal molecules but rather a more direct control of voltage-dependent Ca2+ channels by G proteins. Modulation of Ca2+ channel activity that follows this apparently membrane-confined mechanism has been described to occur in neuronal, cardiac, and endocrine cells. The G protein involved in the hormonal stimulation of Ca2+ channels in endocrine cells may belong to the family of Gi-type G proteins, which are functionally uncoupled from activating receptors by pertussis toxin. The G protein Gs, which is activated by cholera toxin, may stimulate cardiac Ca2+ channels without the involvement of a cAMP-dependent intermediate step. Hormonal inhibition of Ca2+ channels in neuronal and endocrine cells is mediated by a pertussis toxin-sensitive G protein, possibly Go. Whether G proteins act by binding directly to Ca2+ channels or through interaction with as yet undetermined regulatory components of the plasma membrane remains to be clarified.
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PMID:Control of voltage-dependent Ca2+ channels by G protein-coupled receptors. 245 31

G-proteins act as transducers between cell surface receptors activated by extracellular signals and enzymatic effectors which control the concentrations of cytosolic signal molecules such as cAMP, cGMP, inositol phosphates and calcium. The receptor/G-protein-induced changes of the intracellular concentration of such signal molecules correlates with activity changes of various voltage-dependent ion channels. In some instances, cytosolic signal molecules appear to interact directly with ion channels, thereby causing an alteration of ion channel activity. In other instances, signal molecules affect the function of ion channels by activating protein kinases which, in turn, phosphorylate either proteins constituting extracellular signal- and voltage-dependent ion channels or non-identified membranous regulatory components. Recent findings suggest a third, membrane-confined mechanism which does not involve cytosolic signal molecules but a close control of voltage-dependent ion channels by G-proteins. Ion channels that are modulated by extracellular signals according to this newly discovered principle include those for calcium and potassium in neuronal, cardiac and endocrine cells. G-proteins involved in the hormonal stimulation of potassium and calcium channels belong to the family of Gi-type G-proteins which are functionally uncoupled from activating receptors by pertussis toxin. In addition, the cholera toxin-sensitive G-protein, Gs, may directly stimulate cardiac calcium channels. Hormonal inhibition of calcium channels is possibly mediated by Go which, like G-proteins of the Gi-family, is functionally impaired by pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Functional guanine nucleotide-binding proteins in receptor-mediated modulation of voltage-dependent ion channels]. 246 5

1. The mechanism by which acetylcholine (ACh), by stimulation of muscarinic receptors, acts to inhibit activation of the hyperpolarization-activated 'pacemaker' current, if was investigated in isolated rabbit sino-atrial (SA) node myocytes. 2. Intracellular loading with GTP gamma S, a non-hydrolysable analogue of GTP, did not impair the ACh action on if, but made it irreversible. On the other hand, the ACh action on if disappeared after a few minutes of cell loading with GDP beta S, a GDP analogue known to bind to G-proteins and prevent their receptor-stimulated action. Furthermore, incubation of cells in a solution containing pertussis toxin (PTX) led to abolition of the if response to ACh. These results indicate that the inhibitory effect of ACh on if is mediated by G-proteins activated by muscarinic receptors. 3. Intracellular loading with phosphodiesterase (PDE) increased the rate of if current run-down, but did not abolish the inhibitory action of ACh on if. 4. Extracellular perfusion with isobutylmethylxanthine (IBMX), a PDE inhibitor, increased if activation by shifting the current activation range to more positive voltages, as inferred by a three-pulse protocol analysis; in the presence of IBMX, the inhibition of if by ACh was not abolished. 5. The ACh-induced if depression persisted also in cells loaded with cyclic GMP. In these cells, as in those loaded with PDE, the if run-down was fast. 6. Oxotremorine, a muscarinic agonist coupled to adenylate cyclase but not to phosphoinositide turnover in cardiac cells, simulated ACh in its inhibitory action on if. The above results rule against the ACh action being mediated by PDE or by phosphoinositide turnover. 7. To investigate the possible involvement of cyclic AMP as a second messenger in the ACh action on if, we loaded cells with cyclic AMP and IBMX; under these conditions the action of ACh disappeared within a few minutes of whole-cell recording. 8. In cells where the slow inward Ca2+ current (isi) was measured together with if, ACh was seen to depress both currents. 9. In cells superfused with forskolin, the if amplitude on stepping to the half-activation voltage range was enhanced as a consequence of a depolarizing shift of the activation curve; ACh was not effective on if following stimulation by forskolin, but strongly depressed in the same cell the if current stimulated to a similar degree by isoprenaline.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Muscarinic control of the hyperpolarization-activated current (if) in rabbit sino-atrial node myocytes. 247 9

We have studied the activation of the Na+/H+ exchanger which leads to the intracellular alkalinization in cultured bovine aortic endothelial cells stimulated by extracellular ATP. The alkalinization induced by ATP was largely dependent on extracellular Ca2+ and the rate of alkalinization was decreased by about 60% in the absence of extracellular Ca2+. ATP caused a rapid and transient increase and a subsequent sustained increase of the intracellular Ca2+ concentration ([Ca2+]i) in the Ca2+ buffer, while only the rapid and transient increase of [Ca2+]i was observed in the absence of extracellular Ca2+. The Ca2+-depleted cells prepared by incubation in Ca2+-free buffer containing 0.1 mM EGTA showed only a slight increase of [Ca2+]i with no alkalinization on stimulation by ATP. The alkalinization was inhibited by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of protein kinase C, but not by another isoquinoline analogue (HA 1004), which has a less inhibitory effect on the kinase. Phorbol 12-myristate 13-acetate also induced the alkalinization by the activation of the Na+/H+ exchanger. Neither dibutyryl cyclic AMP nor dibutyryl cyclic GMP affected the alkalinization induced by ATP. Treatment of the cells by pertussis and cholera toxins had no effect on the alkalinization. The results suggest that the increase in [Ca2+]i is essential for the ATP-induced activation of the Na+/H+ exchanger in cultured bovine aortic endothelial cells and a protein kinase C-dependent pathway is involved in the activation.
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PMID:Involvement of calcium and protein kinase C in the activation of the Na+/H+ exchanger in cultured bovine aortic endothelial cells stimulated by extracellular ATP. 254 11

Capsaicin, which induces fluxes of sodium, calcium, and potassium ions in a subset of both neonatal and adult rat dorsal root ganglion neurones, increased cyclic GMP (cGMP) levels by a factor of 20 (EC50 0.07 microM) to 10-20 pmol cGMP/mg protein in these cells. Cyclic AMP (cAMP) levels were unaffected. Nonneuronal cells derived from rat ganglia, and both neurones and nonneuronal cells from chick were unresponsive to capsaicin. Capsaicin-induced cGMP elevation in rat dorsal root ganglion (DRG) neurones was unaffected by pertussis toxin, lowered by compounds that block voltage-sensitive calcium channels, and was abolished by the removal of extracellular calcium. Calcium, guanidine, and rubidium fluxes were unaffected by treatment of DRG cells with sodium nitroprusside or dibutyryl cGMP. The cGMP response to capsaicin is thus a function of capsaicin-evoked calcium uptake through voltage-sensitive calcium channels. Elevated cGMP levels do not, however, contribute to capsaicin-evoked ion fluxes or to their desensitisation.
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PMID:Capsaicin-induced ion fluxes increase cyclic GMP but not cyclic AMP levels in rat sensory neurones in culture. 254 99

Angiogenin transiently depresses the cAMP level of rat aortic smooth muscle cells. The dose response is similar to angiogenin activation of the inositol-specific phospholipase C in this cell line [Moore, F. & Riordan, J.F. (1989) Biochemistry. Submitted]. The time course showed a maximal depression (28%) in cAMP at 2 min, followed by a return to that of unstimulated cells by 3.5 min. Angiogenin also inhibited isoproterenol stimulated cAMP formation, but the percentage depression in cAMP (9%) was less than that in cells treated with angiogenin alone (28%). In contrast angiogenin enhanced forskolin stimulation of adenylate cyclase, an effect previously linked with agonist activation of protein kinase C. The effect of angiogenin on cellular cAMP was abolished by pre-incubation with pertussis toxin. Angiogenin had no effect on cellular cGMP. These results are consistent with activation of adenylate cyclase Gi following exposure of the cells to angiogenin and provide further evidence for interaction between cellular signalling pathways.
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PMID:Angiogenin depresses aortic smooth muscle cell cAMP by a pertussis toxin sensitive mechanism. 255 Dec 76

The effect of pertussis toxin (PTX) and the cyclic GMP-lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN) and isosorbide-5-mononitrate (ISMN) in bovine mesenteric artery was investigated. Pretreatment with PTX (100 ng/ml; 2h) induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN and ISMN was seen 10 microM LY83583 markedly reduced the relaxatory effect of all the organic nitroesters. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN and ISMN. However, cGMP seems to play a crucial role in mediating the relaxatory response of all the tested organic nitroesters since LY83583 profoundly suppressed the relaxatory response.
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PMID:Effect of pertussis toxin and the cGMP lowering agent LY83583 on the relaxation induced by nitrates in isolated bovine mesenteric artery. A comparison between glyceryl trinitrate, isosorbide dinitrate and isosorbide 5-mononitrate. 255 77

The heat-stable enterotoxin (STa) of Escherichia coli causes intestinal secretion by stimulating guanylate cyclase, an enzyme believed to be distinct from the STa receptor. Pertussis toxin (PT) has been reported to block the ability of STa to stimulate guanylate cyclase in rat intestinal mucosa (S. A. Epstein, R. A. Giannella, and H. J. Brandwein, FEBS Lett. 203:44-48, 1986). This suggested that a guanine nucleotide regulatory protein (G protein) coupled the STa receptor to guanylate cyclase, a function not previously recognized for G proteins. We sought to explore this phenomenon and, if possible, to identify this G protein. Initial experiments with the human colon carcinoma cell line T84 revealed that higher-than-expected concentrations (1 micrograms/ml) of PT were needed to intoxicate cells, as assessed by ADP-ribosylation of endogenous PT substrate, but that 99 to 100% intoxication could be achieved. Homogenates made from fully intoxicated cells did not differ from controls in basal or STa-stimulated guanylate cyclase activity, and cyclic GMP accumulation in intact T84 cells was not changed by PT treatment. We conclude that a PT-sensitive G protein is not involved in the stimulation of cyclic GMP production by the enterotoxin STa.
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PMID:Failure of pertussis toxin to inhibit activation of guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) in the T84 cell line. 256 75

1. Dissociated adult or fetal rat superior cervical ganglion cells were voltage-clamped through a single patch pipette. The voltage-dependent K+ current, IM (M-current), was maintained by including MgATP in the pipette solution and by buffering the solution pH to 6.7. 2. Bath-applied muscarine (0.4 microM) produced a reversible inhibition of IM. 3. Addition of Gpp(NH)p (200 microM) or GTP-gamma-S (500 microM) to the pipette solution induced a slowly developing inhibition of IM and prevented recovery from subsequent muscarine-induced inhibition. 4. Addition of GDP-beta-S (500 microM) to the pipette solution reduced the amount of IM inhibition produced by 0.4 microM-muscarine by 42% and reduced the associated inward shift of the holding current by 56%. 5. Cells responded normally to muscarine after pre-treatment for 4-27 h with 500 ng ml-1 pertussis toxin (PTx). 6. IM was not diminished by extracellular addition of 1 mM-dibutyryl cyclic AMP, 8-bromo-cyclic AMP or dibutyryl cyclic GMP, or of 10 microM-forskolin. 7. IM was not reduced by inclusion of Li+ (2 mM) or inositol 1,4,5-trisphosphate (IP3, 100 microM) in the patch pipette, nor by ionophoretic injection of IP3 from an inserted micropipette. 8. Addition of 4-beta-phorbol 12,13-dibutyrate (PDBu, 0.5-2 microM) to the extracellular medium partly inhibited IM and reduced an additional component of resting membrane current. This effect was not replicated by 4-alpha-phorbol 12,13-didecanoate. 9. It is concluded that the inhibition of IM by muscarine is mediated through activation of a PTx-insensitive GTP-binding protein. The effect of muscarine appears not to be mediated by cyclic nucleotides or IP3 but may possibly involve the generation of diacylglycerols and activation of protein kinase C.
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PMID:On the transduction mechanism for muscarine-induced inhibition of M-current in cultured rat sympathetic neurones. 268 33

Using freshly isolated bovine adrenal glomerulosa cells we examined the inhibitory effect of atrial natriuretic peptide (ANP) on aldosterone secretion stimulated by agonists that use either the Ca2+-phosphoinositide or cAMP messenger system. In a continuous perifusion system, angiotensin II (AII) induces a prompt initial rise in aldosterone secretion, followed by a sustained secretory response. Both phases of secretion are rapidly and independently inhibited by ANP. The role of two cyclic nucleotides, cGMP and cAMP, as mediators of this ANP-induced inhibition was examined. The effect of 8-bromo-cGMP (1-100 microM) or (Bu)2cGMP (1-50 microM) on the AII-stimulated rate of secretion was studied in a perifusion system. Either analog, whether added early or late, maximally inhibited by 20-30% only the late or sustained phase of aldosterone secretion. The effect of ANP on cellular cAMP content was examined in a static incubation system. Although ANP caused a reduction in the cAMP content of cells stimulated with either AII or ACTH, it had little or no effect on the cAMP levels in cells stimulated with carbachol. In AII- and ACTH-stimulated cells, the relationship between reduced cAMP content and reduced secretion was explored. In the AII-stimulated cell inhibited by ANP, simple restoration of cAMP content with forskolin did not restore the secretory rate. Pertussis toxin treatment blocked the inhibitory effect of ANP on cAMP content, but did not block its inhibition of secretion. In the ACTH-stimulated cell, reversal of the ANP-induced reduction of cAMP with forskolin, partially restored the stimulated rate of secretion, although restoration of cAMP with a 10-fold higher dose of ACTH did not restore the stimulated rate of secretion in the presence of ANP. These results imply that both the ANP-induced rise in cGMP and the ANP-induced decrease in cellular cAMP content may contribute to the inhibition of steroidogenesis. However, these inhibitory messages do not induce either the magnitude or the temporal pattern of inhibition induced by ANP. Thus, in the adrenal multiple messenger systems may underlie the action of ANP.
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PMID:The role of cyclic nucleotides in atrial natriuretic peptide-mediated inhibition of aldosterone secretion. 283 96


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