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)

The present study examines the influence of potassium and sodium ions on guanine nucleotide regulation of adenylate cyclase in various brain regions, including the locus coeruleus (LC), dorsal raphe (DR), ventral tegmentum (VT), hippocampus (HP), frontal cortex (FC), substantia nigra (SN), neostriatum (NS) and cerebellum (CB). Guanine nucleotide regulation of adenylate cyclase was highest in the LC, DR and VT and lowest in NS and CB. Sodium and potassium ions were found to stimulate basal or GTP-activated adenylate cyclase in NS and SN, whereas the cations were found to specifically inhibit guanine nucleotide-stimulated enzyme activity in all other brain regions with the exception of CB, where there was no effect. With regard to stimulation of adenylate cyclase, lithium was more potent than sodium which was more potent than potassium in SN and NS. With regard to inhibition of the enzyme, potassium was equipotent to lithium which was greater than sodium in the other brain regions examined. Both stimulatory and inhibitory effects of cations in the different regions were significant (P less than 0.05) at 30 mM and were maximal at 90-120 mM. Sodium ion inhibition of GTP-stimulated adenylate cyclase in LC and DR was partially blocked by pertussis toxin treatment, whereas cation stimulation in NS was not affected by the toxin. The results demonstrate marked region-specific effects of sodium and potassium on adenylate cyclase, which could occur at either G-proteins or the catalytic unit of the enzyme. The possibility that ion fluxes alter G-protein function is discussed.
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PMID:Sodium and potassium regulation of guanine nucleotide-stimulated adenylate cyclase in brain. 254 4

In the absence of extracellular Ca2+, poly-L-arginine induces little lysozyme release from rabbit polymorphonuclear leukocytes (PMNs). The polycation causes plasma membrane damage, which is evident from the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). In the presence of Ca2+ concentrations higher than 0.2 mM, poly-L-arginine induces a strong lysozyme release that is superimposed on the membrane-damaging effect. The results suggest that poly-L-arginine permeabilizes the plasma membrane, enabling Ca2+ to enter the cell, which results in the exocytotic release of granule constituents. The GTP analog GTP gamma S shifts the Ca2+ requirement of exocytosis to slightly higher concentrations, whereas it completely inhibits poly-L-arginine-induced LDH release. Pertussis toxin gives a moderate inhibition, and La3+ completely inhibits poly-L-arginine-induced enzyme release. Whereas poly-L-arginine alone induces little superoxide generation in rabbit PMNs, there is a synergistic enhancement of superoxide production when GTP gamma S and poly-L-arginine are present together. Guanine nucleotides apparently have a modulating effect on the actions of poly-L-arginine on the PMN, but the nature of this effect remains to be determined.
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PMID:Permeabilization and calcium-dependent activation of rabbit polymorphonuclear leukocytes by poly-L-arginine. 254 93

The solubilized D2-dopamine receptor from bovine striatum exhibits high and low affinity states for dopaminergic agonists. Guanine nucleotides and pertussis toxin convert the solubilized receptor from a high affinity state to a low one. A D2-receptor preparation partially purified by affinity chromatography on a haloperidol adsorbent, exhibited agonist-stimulated GTPase activity. [32P]ADP-ribosylation by pertussis toxin of this receptor preparation resulted in the specific labeling of two protein bands corresponding to mol. wts of 39 and 41 kd, in SDS-PAGE. Association of these G-proteins with the receptor was specifically inhibited by Gpp(NH)p. Immunoblot analysis of these G-proteins indicated that the 41- and 39-kd protein bands are analogous to brain Gi and Go respectively. These experiments demonstrate that two distinct pertussis toxin-sensitive G-proteins are functionally associated with bovine striatum D2-dopamine receptor.
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PMID:Association of two pertussis toxin-sensitive G-proteins with the D2-dopamine receptor from bovine striatum. 257

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

Guanine nucleotide-binding regulatory proteins similar to Gs and Gi may be involved in the activation of phospholipases C and A2 by hormones and other ligands. The binding of hormones to receptors that activate phospholipase C is decreased by guanine nucleotides and these hormones also stimulate a high-affinity GTPase activity in cell membranes. Effects of hormones on phospholipase C activity in cell-free preparations are dependent on the presence of guanine nucleotides. In addition, fluoride and nonhydrolyzable GTP analogs activate phospholipases in a manner that can be blocked by GDP beta S. The putative guanine nucleotide-binding regulatory protein that appears to be involved in activation of phospholipase C is sensitive to pertussis toxin in some cells but not in others.
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PMID:Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones. 283 62

Guanine nucleotides have been examined as to their effects on subclass-specific excitatory amino acid receptor-ligand interactions. Guanine nucleotides selectively inhibit L-[3H]glutamate binding to the N-methyl-D-aspartate (NMDA) recognition site while showing a lesser effect on [3H]kainate, [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and sodium-dependent L-[3H]glutamate binding. Of the series of guanine nucleotides tested in the inhibition of NMDA-specific L-[3H]glutamate binding, GTP, GDP, 5'-guanylylimidodiphosphate and 5'-guanylylmethylenediphosphate were significantly more potent than GMP, cyclic GMP and guanosine. Scatchard analysis indicates that the GTP inhibition (IC50 = 28 microM) of this NMDA-specific L-[3H]glutamate binding results from a decrease in the affinity of L-glutamate for the NMDA receptor whereas no alteration in the number of binding sites is observed. A kinetic analysis indicates that this decrease in affinity may be attributed to a decrease in association rate whereas no change in dissociation rate is observed. GTP (25 microM) lowers the affinities of both NMDA agonists (NMDA, L-glutamate, L-aspartate, and L-homocysteate) and antagonists (D-2-amino-5-phosphonovalerate, D-2-amino-7-phosphonoheptanoate, and D-2-aminoadipate). Pretreatment of the synaptic plasma membranes with either pertussis or cholera toxin had no significant effect on the GTP inhibition of NMDA-specific L-[3H] glutamate binding. The data suggest that guanine nucleotides can negatively modulate the NMDA receptor; however, the mechanism of this modulation is unclear.
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PMID:Effects of guanine nucleotides on N-methyl-D-aspartate receptor-ligand interactions. 284 50

Guanine nucleotide binding proteins were examined for their influence in developmental and adaptive models of adrenergic actions in the heart. In primary cultures of rat cardiac myocytes, the positive chronotropic response to the alpha-agonist, phenylephrine, changes to negative when these cells are grown with and innervated by sympathetic nerves from the paravertebral chain. Innervated cells have significantly more G protein, as determined by the ADP-ribosylation reaction catalyzed by pertussis toxin, which is linked functionally to the negative chronotropic response. Adult canine Purkinje fibers that respond to phenylephrine with a decrease in automaticity are also linked biochemically and functionally to a G protein that serves as a pertussis toxin substrate. Fibers that increase in automaticity after exposure to phenylephrine, either under control conditions (a minority of fibers) or after prior exposure to pertussis toxin (a majority of fibers), have markedly reduced levels of G. A G protein was also shown to be important in the blunted adrenergic responsiveness that characterizes congestive heart failure in human subjects. In this model, the receptor complex is beta-adrenergic and the involved G protein is a cholera toxin substrate. Gs is reduced in the lymphocytes of patients with congestive heart failure and increases toward normal after successful therapy. These observations highlight the important roles that G proteins have in adrenergic actions of the heart both with respect developmental and adaptive changes.
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PMID:G protein-adrenergic interactions in the heart. 284 13

Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (Ni) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p] greater than GTP greater than GDP greater than GMP. Scatchard analysis 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+. When pancreatic acini were treated with 1 microgram/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Gpp(NH)p further decreased somatostatin binding to islet-activating protein (IAP)-treated acinar membranes. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. Furthermore, exposure of acini to IAP caused ADP ribosylation of a membrane protein with Mr = 41,000 in parallel to the inhibition of cAMP accumulation in acini. The present results suggest, therefore, that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor.
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PMID:Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes. 288 15


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