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)

ADP ribosylation in the presence of cholera or pertussis toxin indicated the presence of G-proteins in Nb2 cell membranes. Two protein bands, with mol wt of 43.5K and 46.5K, were radiolabeled by cholera toxin, while a single protein (41.5K mol wt) was ADP ribosylated by pertussis toxin. Northern hybridization of total RNA from Nb2 cells with specific cDNA probes indicated the presence of mRNA transcripts encoding Gs, Gi2, Go, and, to a lesser extent, Gi3. A characteristic of receptors coupled to G-proteins is that their binding properties are regulated by guanine nucleotides. The binding of [125I]human GH to the lactogen receptor as well as the binding of [125I]IL-2 to the IL-2 receptor were decreased in a dose-dependent manner by GTP, GDP, and the analog guanosine 5'-O-(3-thiotriphosphate). GMP, however, had no effect. The addition of pyruvate kinase and phosphoenolpyruvate to regenerate GTP from GDP greatly increased the apparent potency of GTP. Cholera toxin inhibited PRL- and interleukin-2-stimulated DNA synthesis and cell proliferation in the Nb2 cells. In contrast, pertussis toxin had a differential effect on PRL- and IL-2-stimulated cells. Pertussis toxin, at an optimal concentration of 0.01 ng/ml, significantly enhanced the stimulatory effects of PRL on DNA synthesis (P less than or equal to 0.01; n = 9) and cell proliferation (P less than or equal to 0.05; n = 9) compared with the effect of PRL alone. However, at higher concentrations the toxin inhibited PRL-stimulated DNA synthesis and cell proliferation. Complete inhibition was achieved with 1000 ng/ml toxin. In contrast to the biphasic effect on PRL-stimulated cells, pertussis toxin was only weakly inhibitory to cells treated with IL-2. At the highest concentration tested, pertussis toxin (1000 ng/ml) inhibited IL-2-stimulated DNA synthesis and cell growth by only 30-35%. (Bu)2cAMP (IC50 = 0.019 mM) or methylxanthine (MIX; IC50 = 0.25 mM) also inhibited PRL-stimulated DNA synthesis. In the absence of mitogen, neither agent, from 0.0001-1 mM, had any effect on DNA synthesis. Similarly, IL-2-stimulated DNA synthesis in Nb2 cells was inhibited by (Bu)2cAMP (IC50 = 0.019 mM) or MIX (IC50 = 0.072 mM). However, MIX was approximately 3 times as potent in inhibiting the cell response to IL-2 as that to PRL. The susceptibility of Nb2 cells to both bacterial toxins suggests a role for G-proteins in regulating PRL- or IL-2-stimulated mitogenesis in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:G-proteins modulate prolactin- and interleukin-2-stimulated mitogenesis in rat Nb2 lymphoma cells. 246 72

125I-Galanin was cross-linked to receptor in Rin m 5F cell membranes using the bifunctional reagent disuccinimidyl tartarate. Regardless of the presence of reducing agents, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cross-linked galanin-receptor complexes revealed the presence of a radioactive band at Mr 57,000. Excess unlabeled galanin completely inhibited the labeling of the band while other regulatory peptides had no effect. Labeling of the Mr 57,000 complex was abolished by galanin concentration from 10(-9) to 10(-6) M (IC50 = 5 X 10(-9) M). Initial incubation with 125I-galanin in the presence of increasing concentrations of guanyl-5'-yl imidodiphosphate (GMP-P(NH)P) (10(-7) to 10(-4) M) also inhibited the labeling of the Mr 57,000 complex. Moreover, pretreatment of membranes with pertussis toxin before formation of the covalent galanin-receptor complex, dramatically reduced the labeling of the Mr 57,000 species. Covalent Mr 57,000 galanin-receptor complexes solubilized by Triton X-100 bound specifically to wheat germ agglutinin-concanavalin A-, and soybean-coupled Sepharose, supporting the glycoproteic nature of the galanin receptor. Assuming one molecule of 125I-galanin (Mr 3,000) was bound per molecule of protein, these results suggest that the pancreatic galanin receptor is a glycoprotein with a Mr of 54,000 bearing the recognition site for the ligand and which is coupled with a pertussis toxin-sensitive G protein in the plasma membrane.
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PMID:Galanin receptor in the rat pancreatic beta cell line Rin m 5F. Molecular characterization by chemical cross-linking. 247 48

The role of guanine nucleotide-binding proteins (G-proteins), acting as transducers between membranous receptors activated by extracellular signals and enzymatic effectors controlling the concentrations of intracellular signal molecules, is well established. G-proteins are also involved in the hormonal modulation of voltage-dependent Ca2+ channels. In various cell types, the increase in intracellular signal molecules via G-protein-coupled receptors causes activation of protein kinases which may stimulate or inhibit voltage-dependent Ca2+ channels. For example, voltage-dependent Ca2+ channels of cardiac and skeletal myocytes are stimulated by cyclic adenosine monophosphate (cAMP)-dependent protein kinase. Other protein kinases, i.e., cyclic guanosine monophosphate (cGMP)-dependent protein kinase and Ca2+/phospholipid-dependent protein kinase C, also appear to be involved in the hormonal modulation of Ca2+ channels. According to this principle, G-proteins exert a distant control of ion channel activity. In addition, there appears to exist another mechanism which does not involve intracellular signal molecules or protein kinases stimulated by intracellular signal molecules. The only signal transduction components identified so far include receptors, G-protein and Ca2+ channels. Ca2+ channel modulations following this apparently membrane-confined mechanism have been described to occur in neuronal, endocrine and cardiac cells. Hormonal inhibition of Ca2+ channels in neuronal and endocrine cells is mediated by a pertussis-toxin-sensitive G-protein, possibly G0. The G-protein involved in the hormonal stimulation of Ca2+ channels in adrenocortical and pituitary cells may represent a pertussis-toxin-sensitive G-protein of the Gi-type. The choleratoxin-sensitive G-protein, Gs, may stimulate cardiac Ca2+ channels without the involvement of a cAMP-dependent intermediate step.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Bidirectional hormonal modulation of voltage dependent ca2+ channels]. 254 33

The intracellular messengers that seem to be involved in renin secretion (RS) from juxtaglomerular cells (JG) are calcium (Ca), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Unlike the majority of secretory systems, an increase in intracellular Ca concentration and calmodulin and protein kinase C activation inhibit RS. The intracellular Ca concentration in JG cells can be modified if: 1) the normal mechanisms of Ca extrusion of these cells is altered; 2) the calcium output is blocked by lanthanum; 3) the function of the voltage-sensitive Ca-channels is modified; 4) uptake or liberation of Ca from endoplasmic reticulum is modified; 5) plasmatic membrane is bypassed with calcium ionophores such as A 23187. 6) JG cells are stimulated by hormones that increase Ca and activate protein kinase C such as angiotensin II, vasopressin or alpha-1 adrenergic agonists; 7) extracellular Ca concentration increases or decreases. RS is stimulated by dibutyryl cAMP, cAMP phosphodiesterase inhibitors and by hormones and agents that activate adenylate cyclase (beta adrenergic agonists, bradykinin, histamine, forskolin and ethylcarboxamide adenosine). On the contrary, RS is inhibited by hormones and agents that inhibit adenylate cyclase such as: alpha-2 adrenergic agonists, neuropeptide Y, angiotensin II and cyclohexyladenosine. Pertussis toxin increases basal RS, blocks the inhibition by agents and hormones which inhibit adenylate cyclase and potentiate the stimulation produced by beta-adrenergic agonists. In JG cells, atrial natriuretic peptide inhibits RS, increases cGMP and decreases cAMP. The increase in cGMP correlates well with the inhibition of RS.
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PMID:[Intracellular messengers in the regulation of renin secretion]. 255 Oct 26

1. Voltage-activated Ca2+ channel currents were recorded from cultured rat dorsal root ganglion (DRG) neurones using the whole-cell clamp technique with Ba2+ as the charge carrier. 2. Inclusion of the GTP analogue guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S, 500 microM) or guanylylimidodiphosphate (GMP-PNP, 500 microM) or GTP itself (1 mM) in the patch pipette solution resulted in a smaller, slowly activating Ca2+ channel current which did not inactivate during a 100 ms voltage step. This current was inhibited by CdCl2 (10-100 microM) and omega-conotoxin (1 microM). 3. Nifedipine (5 microM), (-)-(R)-201-791 (5 microM), D600 (10 microM), and diltiazem (30 microM) inhibited Ca2+ channel currents recorded from control neurones, although in some cells a biphasic response was observed, with an initial increase preceding the inhibition of the currents. In the presence of internal GTP-gamma-S, at a holding potential (VH) of -80 mV, only potentiation of the Ca2+ channel current was observed in the presence of all three Ca2+ channel ligands. Internal GMP-PNP, while less effective than GTP-gamma-S, also resulted in D600 showing an agonist response. Similarly, in the presence of internal GTP (1 mM), (-)-(R)-202-791 gave a prolonged agonist response. 4. Nifedipine, whether acting as an antagonist in control cells or as an agonist in GTP-gamma-S-containing cells, induced a shift to more hyperpolarized potentials of the steady-state inactivation curves. 5. Potentiation of Ca2+ channel currents induced by D600 in GTP-gamma-S-containing cells, was not observed when the neurones were pre-treated with pertussis toxin. The presence of internal GDP-beta-S (500 microM) did not significantly alter the maximum inhibitory action of D600 compared with controls. However, 1 mM-GDP-beta-S increased the rate of onset of inhibition by (-)-(R)-202-791. 6. Depolarizing VH to -30 mV accelerated the onset of inhibition induced by the Ca2+ channel ligands in control cells. In the presence of internal GTP-gamma-S at VH -30 mV, biphasic responses were produced by all the Ca2+ channel antagonist ligands with initial stimulation for 1-2 min being followed by inhibition of the Ca2+ channel currents. 7. The agonist actions of (+)-(S)-202-791 were potentiated by the presence of internal GTP-gamma-S. 8. The expression of an agonist response to (-)-(R)-202-791 induced by internal GTP-gamma-S was also present in sympathetic neurones cultured from adult rat superior cervical ganglion (SCG).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interaction between calcium channel ligands and guanine nucleotides in cultured rat sensory and sympathetic neurones. 255 37

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.
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PMID:Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line. 256 5

Neurons in hippocampal and striatal cell cultures respond to adenosine with an inhibitory potassium current. This response disappears during whole-cell patch-clamp recording in which the cell is filled with minimal saline. We have found that this loss of sensitivity to adenosine can be prevented by including 100 microM GTP in the patch electrode filling solution. GDP is less effective than GTP in supporting the adenosine response, while GMP has little, if any, effect. Treatments known to inhibit GTP-binding proteins (G-proteins) block the adenosine-activated potassium current: The adenosine response is inhibited by including poorly metabolized analogs of guanine nucleotides along with GTP in the recording electrode. Diphosphate and triphosphate analogs appear to achieve this effect through different mechanisms. The adenosine response is also blocked by incubating cultures in islet-activating protein (pertussis toxin), an inhibitor of a class of G-protein. Thus, our data implicate a G-protein in the activation of a potassium current by adenosine. Intracellular ATP can increase the effectiveness of GMP, GDP, or low concentrations of GTP, suggesting that even during internal dialysis, neurons can maintain GTP levels through phosphotransferase reactions. Intracellular ATP also appears to suppress an outward current that is different from the adenosine-activated current. Raising intracellular cAMP levels either with bath-applied forskolin or by including a cAMP analog in the recording electrode did not alter the adenosine response. These results indicate that a G-protein is involved in the coupling between the adenosine receptor and a potassium channel, and that this coupling is not mediated by cAMP.
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PMID:Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons. 282 65

To investigate whether somatostatin receptors couple to guanine nucleotide inhibitory protein, Ni, on rat pancreatic acinar membranes, the effects of guanine nucleotide analogs or pretreatment of acini with islet activating protein (IAP), pertussis toxin on labeled somatostatin binding were examined. Guanine nucleotides reduced labeled somatostatin binding to acinar membranes up to 80%, with rank order of potency being guanyl-5'-yl imidodiphosphate (Gpp(NH)p) greater than GTP greater than GDP greater than GMP. Scatchard analysis of the labeled somatostatin binding revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+ and Na+ also reduced labeled somatostatin binding. Furthermore, inhibitory effects of 100mM Na+ and Gpp(NH)p were additive in reducing labeled somatostatin binding. A half maximal inhibitory concentration of Gpp(NH)p was decreased to 10(-7)M in the presence of 100mM Na+ and 5mM Mg2+ as compared to 10(-6)M in the presence of 5mM Mg2+ alone. Results therefore suggest that Gpp(NH)p requires Mg2+ for Ni activation and Na+ increases sensitivity of Ni to guanine nucleotide analogs. When pancreatic acini were treated for 4 hours with varying concentrations of IAP, which has been shown to uncouple Ni-mediated communication between inhibitory receptors and adenylate cyclase catalytic unit, subsequent labeled somatostatin binding to the acinar membranes was decreased in a dose dependent manner. These results indicate that somatostatin receptors on pancreatic acinar membranes couple to guanine nucleotide inhibitory protein, Ni and thus somatostatin probably functions in the pancreas to regulate intracellular signal transduction via Ni.
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PMID:[Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on rat pancreatic acinar membranes]. 282 26

The neuropeptide bombesin acts on a variety of target cells to stimulate the processes of secretion and cell proliferation. In this study we determined whether bombesin receptors interact with known guanine nucleotide-binding proteins in four different cell types: GH4C1 pituitary cells, HIT pancreatic islet cells, Swiss 3T3 fibroblasts, and rat brain tissue. Maximal concentrations of nonhydrolyzable GTP analogs decreased agonist binding to bombesin receptors in membranes from all four sources. In GH4C1 and HIT cell membranes GTP analogs inhibited bombesin receptor binding with IC50 values of about 0.1 microM, whereas GDP analogs were approximately 10-fold less potent. In contrast, GMP and the nonhydrolyzable ATP analog adenylyl-imidodiphosphate had no effect at 100 microM. Equilibrium binding experiments in GH4C1 and HIT cell membranes indicated a single class of binding sites with a dissociation constant (Kd) for [125I-Tyr4]bombesin of 24.4 +/- 7.0 pM and a binding capacity of 176 +/- 15 fmol/mg protein. Guanine nucleotides decreased the apparent affinity of the receptors without significantly changing receptor number. Consistent with this observation, guanine nucleotides also increased the rate of ligand dissociation. Pretreatment of GH4C1 or HIT cells with either pertussis toxin (100 ng/ml) or cholera toxin (500 ng/ml) for 18 h did not affect agonist binding to membrane bombesin receptors, its regulation by guanine nucleotides, or bombesin stimulation of hormone release. Although pertussis toxin pretreatment has been reported to block bombesin stimulation of DNA synthesis in Swiss 3T3 cells, it did not alter the binding properties of bombesin receptors in Swiss 3T3 membranes or inhibit the rapid increase in intracellular [Ca2+] produced by bombesin in these cells. In summary, our results indicate that the bombesin receptor interacts with a guanine nucleotide-binding protein which exhibits a different toxin sensitivity from those which regulate adenylate cyclase as well as those which couple some receptors to phospholipases.
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PMID:The bombesin receptor is coupled to a guanine nucleotide-binding protein which is insensitive to pertussis and cholera toxins. 283 Feb 64

Isolated human polymorphonuclear (PMN) leukocyte plasma membranes express high affinity (mean Kd = 0.12 nM) and low affinity (mean Kd = 50 nM) receptors for the chemotactic factor leukotriene B4 (5(S),12(R)-dihydroxy-eicosa-6,14 cis-8,10 trans-tetraenoic acid; LTB4) that are similar to those on intact PMN leukocytes. A portion of high affinity LTB4-R on PMN leukocyte membranes were converted to the low affinity state by GTP (mean +/- SE = 28.6 +/- 14.0%) and nonhydrolyzable GTP analogues, such as 5'-guanylylimidodiphosphate (GMP-PNP), in a concentration-dependent, nucleotide-specific, and reversible manner, without altering the intrinsic binding affinities of either class. [3H]GMP-PNP bound specifically to one class of receptors (mean Kd = 13 nM) on PMN leukocyte membranes. The interdependence of the LTB4-binding membrane protein and guanine nucleotide-binding protein was suggested by the capacity of LTB4 to enhance by a maximum of 150% the binding of [3H]GMP-PNP to PMN leukocyte membranes by increasing the number, but not altering the affinity, of receptors for GMP-PNP. Pertussis toxin, but not cholera toxin, reversed the enhancement of binding of [3H]GMP-PNP produced by LTB4. Guanine nucleotide-binding proteins and high affinity LTB4-R thus exhibit a mutual regulation that differs mechanistically from that of peptide chemotactic factor receptors on PMN leukocytes.
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PMID:Selective modulation by guanine nucleotides of the high affinity subset of plasma membrane receptors for leukotriene B4 on human polymorphonuclear leukocytes. 283 4


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