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)

Intracellular recordings were obtained from the basolateral amygdala in in vitro rat brain slice preparations to examine whether gamma-aminobutyric acid (GABA)B receptors are altered after in vivo kindling-induced epileptogenesis. Stimulating the stria terminalis evoked excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials in control neurons, and epileptiform bursting or enhanced EPSPs, but no IPSPs, in neurons from animals, 4 to 8 weeks after the last kindled seizure. Baclofen (0.1 nM-100 microM) depressed EPSPs in control and kindled basolateral amygdala neurons, but the EC50 appeared to be shifted 100-fold from 5 nM in control to 500 nM in kindled neurons. Further analysis suggested a high-affinity component may be affected in kind led neurons. The absence of IPSPs in kindled neurons could not account for this shift, because effects of baclofen on EPSP amplitude were reduced in kindled animals even when GABAA receptors were blocked with bicuculline methiodide (30 microM) and postsynpatic GABAB receptors with intracellular guanosine 5'-O-3-thiotriphosphate (10 mM); 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (10 microM) was also present to block bicuculline methiodide-induced bursting. Membrane responses to exogenously applied N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid were not affected by baclofen. Baclofen also hyperpolarized basolateral amygdala neurons and reduced membrane input resistance with an EC50 of 1 microM in control and kindled neurons. Post- but not presynaptic effects of baclofen were blocked by 2-hydroxy-saclofen (100 microM) and pertussis toxin pretreatment. In conclusion, kindling-induced epileptogenesis reduces the sensitivity of presynaptic GABAB receptors, an effect which may contribute to the enhancement of excitatory transmission in kindled animals. Furthermore, different pharmacological properties of pre- and postsynaptic receptors in the amygdala suggest two distinct populations of GABAB receptors whose long-lasting responses to kindling-induced seizures are different.
J Pharmacol Exp Ther 1992 Sep
PMID:Epileptogenesis reduces the sensitivity of presynaptic gamma-aminobutyric acidB receptors on glutamatergic afferents in the amygdala. 132 20

We have examined the isolated postsynaptic density (PSD) fraction for the presence of a G protein. First, we found specific binding of guanosine 5'-[gamma-[35S]thio]triphosphate to the PSD. Second, pertussis toxin-activated ADP-ribosylation of the isolated PSD fraction resulted in the appearance of a G protein with an apparent molecular mass of 41 kDa, and two G proteins with apparent molecular masses of 41 kDa and 39 kDa in synaptic membrane (SM) fraction and total homogenate (H). The amount of the 41-kDa G protein per unit protein was in the order of SM greater than H greater than PSD. Anti-G(i0 antibodies recognized the 41-kDa G protein in both PSD and SM, whereas anti-G(o) antibodies reacted with the 39-kDa G protein in the SM. The absence of G(o) protein in the PSD suggested that there was no contamination with SM. Moreover, unlabeled PSD incubated with an extract of SM that contained the labeled G proteins resulted in no label in the subsequently reisolated PSD, suggesting that the G protein found in the PSD was not due to adsorption of the G protein onto the PSD during its isolation from the SM. PSD pretreated with EGTA gave an 11-fold increase in the ADP-ribosylation reaction of the G(i) protein; similar effects on the G(i) and G(o) proteins of SM were obtained. Restoration of Ca2+/calmodulin to the PSD, but not of either Ca2+ or calmodulin alone, removed the effect of EGTA, indicating a strong complex formation between G(i) and Ca2+/calmodulin that decreased the ADP-ribosylation reaction. Preincubation with the Ca(2+)-channel blocker nifedipine decreased the ADP-ribosylation reaction in the PSD. We conclude that G(i) is present in the PSD, that it may interact with calmodulin and that it is involved in the regulation of voltage-dependent Ca2+ channel. We present a theory of the involvement of the G protein and calmodulin in postsynaptic neurophysiological events.
Proc Natl Acad Sci U S A 1992 Sep 15
PMID:Occurrence of the alpha subunits of G proteins in cerebral cortex synaptic membrane and postsynaptic density fractions: modulation of ADP-ribosylation by Ca2+/calmodulin. 132 62

Coronary stenosis was induced in rats to determine whether chronic coronary artery constriction resulted in impairment of cardiac pump performance, alterations in alpha 1-adrenoreceptor signal transduction, and inadequate myocardial hypertrophy, and these parameters were examined 6 mo later. A 50% reduction in coronary diameter was associated with an elevation in left ventricular end-diastolic pressure, whereas left ventricular peak systolic pressure, rate of pressure rise and decay were reduced. The hypertrophic response was modest, since statistically significant increases of 11% and 23% in left and right ventricular weights were measured. Radioligand binding documented an 18% and a 38% statistically significant reduction in alpha 1-adrenoreceptor density of the left and right myocardium, respectively. ADP ribosylation of the 41-kDa substrate by pertussis toxin showed a 16% significant decrease of this parameter in the left myocardium. Moreover, a 29% decrease in norepinephrine stimulated phosphoinositol turnover was seen in myocytes, and this change was statistically significant. The depressed generation of intracellular second messengers linked to the alpha 1-adrenoreceptors was found in conjunction with a 19% significant reduction in myocardial norepinephrine content. In conclusion, the long-term effects of coronary stenosis involve impaired transduction of adrenergic signals, which, in combination with constraints on myocardial growth, may participate in the onset of ventricular dysfunction in this model.
Am J Physiol 1992 Sep
PMID:Chronic coronary arterial stenosis impairs alpha 1-adrenoreceptor signaling and cardiac performance in rats. 132 38

The signal transduction systems of the neuropeptide Y (NPY) Y1 receptor were studied in SK-N-MC human neuroblastoma cells. NPY induced an increase in intracellular calcium ion concentration ([Ca2+]i) and inhibition of forskolin-stimulated cyclic AMP accumulation, which were mediated through Y1 receptors. One-min preincubation of cells with phorbol 12-myristate 13-acetate (PMA) inhibited both signal transductions dose-dependently, but its effect on [Ca2+]i was about 100-fold more potent than that on cyclic AMP. PMA had no effect on [125I]BH-NPY binding in SK-N-MC cells and hardly inhibited the endothelin-1-induced increase in [Ca2+]i. Pertussis toxin also inhibited the NPY-induced [Ca2+]i increase 30-fold more effectively than the NPY-mediated inhibition of cyclic AMP accumulation. These results indicate that Y1 receptors in SK-N-MC cells couple to two signal transduction systems that have different sensitivities to phorbol ester and pertussis toxin treatments.
Biochem Biophys Res Commun 1992 Sep 30
PMID:Two different signal transductions of neuropeptide Y1 receptor in SK-N-MC cells. 132 39

Many cells develop enhanced adenylate cyclase activity after prolonged exposure to drugs that acutely inhibit the enzyme and it has been suggested that this adaptation may be due to an increase in Gs alpha. We have treated wild-type and Gs alpha-deficient cyc- S49 mouse lymphoma cells with a stable analogue (SMS 201-995) of the inhibitory agonist somatostatin. After incubation with SMS for 24 h, the forskolin-stimulated cAMP synthetic rate in intact cyc- cells was increased by 76%, similar to the increase found in the wild-type cells. Forskolin-stimulated adenylate cyclase activity in the presence of Mn2+ was also increased in membranes prepared from SMS-treated cyc- cells; however, guanine nucleotide-mediated inhibition of adenylate cyclase activity was not changed despite a small decrease in inhibitory Gi alpha subunits detected by immunoblotting. Pretreatment of cyc- cells with pertussis toxin prevented SMS from inducing the enhancement of forskolin-stimulated cAMP accumulation in intact cells. After chronic incubation of cyc- cells with SMS, exposure to N-ethylmaleimide, which abolished receptor-mediated inhibition of cAMP accumulation, did not attenuate the enhanced rate of forskolin-stimulated cAMP synthesis compared to N-ethylmaleimide-treated controls. These results with cyc- cells demonstrate that an adaptive increase in adenylate cyclase activity induced by chronic treatment with an inhibitory drug can occur in the absence of expression of Gs alpha.
Cell Signal 1992 Sep
PMID:Prolonged activation of inhibitory somatostatin receptors increases adenylate cyclase activity in wild-type and Gs alpha-deficient (cyc-) S49 mouse lymphoma cells. 132 4

NIH-3T3 fibroblasts have been transfected with human serotonin 5-HT1A receptors. Clonal cell lines expressed between 40 and 500 fmol receptor/mg. 5-HT1A agonists strongly inhibited nonstimulated- as well as forskolin- or isoproterenol-stimulated adenylyl cyclase. The effects of 5-HT1A receptor activation on cell growth were investigated. 5-HT1A agonists accelerated cell division, generated foci, and increased DNA synthesis. The stimulation of [3H]thymidine incorporation was much stronger when tyrosine kinase receptors were activated concomitantly. Cyclic AMP (cAMP) elevating agents inhibited DNA synthesis induced by all mitogens tested. The mitogenic activity of 5-HT1A agonists did not seem to be linked to adenylyl cyclase inhibition because 1) we were not able to measure any decrease in intracellular cAMP levels under the conditions of DNA synthesis assay and 2) 2',5'-dideoxyadenosine, which strongly inhibited adenylyl cyclase, was not mitogenic and did not modify the mitogenic effects of 5-HT1A agonists. Pertussis toxin completely blocked potentiation of epidermal growth factor effect induced by 8-hydroxy-di-(n-propyl)aminotetralin, a 5-HT1A agonist, but only partially blocked the one induced by insulin. In conclusion, in transfected NIH-3T3 cells, transforming and mitogenic effects of 5-HT1A agonists involve a pertussis toxin-sensitive G protein but do not seem to be linked to adenylyl cyclase inhibition.
Mol Biol Cell 1992 Sep
PMID:Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis. 133 92

1. In the present study, we demonstrate that leukotriene B4 (LTB4) has the ability to activate the human neutrophil 5-lipoxygenase (5-LO). 2. Stimulation of neutrophils with 30 nM 14,15-dideuterio-LTB4 (D2-LTB4) failed to induce the synthesis of LTB4 from endogenous arachidonic acid (AA), but stimulated the formation of LTB4 from 3.3 microM exogenous AA, as determined by GC-MS analysis. 3. The stimulatory effect of LTB4 on 5-LO activity was further examined with an alternative substrate; LTB4 time- and dose-dependently stimulated the 5-LO-mediated conversion of exogenous 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoate (15-HpETE) into 5(S),15(S)-dihydroxy-6,8,11,13,-(E,Z,Z,E)-eicosatetraenoate (5,15-DiHETE), with a threshold effect at 300 pM. 4. The ability of LTB4 to activate the 5-LO showed structural specificity, since LTB4 was found to be 100 times more potent than omega-hydroxy-LTB4, and 300 times more potent than its delta 6-trans-12-epi-isomer. 5. The LTB4-induced 5-LO activation was effectively inhibited by MK-886 (an inhibitor of 5-LO translocation), by pertussis toxin, and by the LTB4 receptor antagonist, LY-223982. 6. These results demonstrate that the binding of LTB4 to its cell-surface receptor results in 5-LO activation in a process mediated by pertussis toxin-sensitive guanine nucleotide-binding proteins. Our data also suggest that the underlying mechanism involves a translocation of the 5-LO to the membrane. These findings raise the possibility that LTB4 produced by phagocytes may positively feedback on its own synthesis.
Br J Pharmacol 1992 Sep
PMID:Activation of the human neutrophil 5-lipoxygenase by leukotriene B4. 133 Jan 61

The F11 cell line is a fusion product of cells of mouse neuroblastoma cell line N18TG-2 with embryonic rat dorsal-root ganglion (DRG) neurons. Previous biochemical results suggest that they express mu- and delta-opioid receptors that are negatively coupled to adenylate cyclase. The present study provides direct agonist-binding and electrophysiologic evidence of mu and delta, but not kappa, receptor expression in F11 cells. Radioligand binding assays show that F11 cell membranes bind the mu- and delta-opioid receptor agonists, DAGO and DPDPE with Kd = 4.5 and 4.9 nM and Bmax = 111 and 195 fmol/mg, respectively. Tight-seal patch-clamp recordings of F11 cells after several days in a differentiating culture medium (low serum, cyclic AMP and nerve growth factor) showed that: (i) the outward K+ current during pulsed depolarization in most of these cells was increased by either DAGO or DPDPE, but none were responsive to both opioids or to the kappa-opioid receptor agonist, U-50,488H. The response was blocked by relevant receptor antagonists, naloxone, beta-funaltrexamine or naltrindole; (ii) cells without processes responded neither to DAGO nor to DPDPE; (iii) treatment with pertussis toxin blocked all opioid-induced increases in outward K+ current. The opioid-induced increase in voltage-dependent membrane K+ current in F11 cells resembles the inhibitory effect elicited by mu- and delta-opioid agonists in primary cultures of mouse DRG neurons.
Brain Res 1992 Sep 11
PMID:F11 neuroblastoma x DRG neuron hybrid cells express inhibitory mu- and delta-opioid receptors which increase voltage-dependent K+ currents upon activation. 133 Feb 16

Cultured endothelium derived from three microvascular fractions of human brain was used to characterize adrenergic receptors coupled to adenylate cyclase activity. Catecholamines (norepinephrine, epinephrine) and their analogs (isoproterenol, phenylephrine, 6-fluoronorepinephrine) dose-dependently stimulated endothelial production of cAMP. Antagonists for beta 1 and beta 2 receptors (propranolol, atenolol, and butoxamine) and for alpha 1-receptors (prazosin) dose-dependently blocked cAMP formation induced by the tested adrenergic agonists. Clonidine, an alpha 2 > alpha 1-agonist, also inhibited isoproterenol-stimulated production of cAMP while yohimbine (alpha 2 > alpha 1 antagonist) augmented the norepinephrine or epinephrine-induced accumulation of cAMP. Cholera toxin-induced ADP ribosylation of the stimulatory guanine nucleotide binding protein (Gs) abolished the stimulatory effect of norepinephrine, epinephrine, phenylephrine or 6-fluoronorepinephrine on cAMP formation. ADP ribosylation of the inhibitory guanine nucleotide binding protein (Gi) by pertussis toxin had no effect on either phenylephrine- or 6-fluoronorepinephrine-induced production of cAMP while it increased the norepinephrine and epinephrine-induced accumulation of cAMP. These findings represent the first documentation of beta 1-, beta 2-, alpha 1 and alpha 2-adrenergic receptors linked to adenylate cyclase in endothelium derived from human brain microvasculature. These data also indicate that activation of endothelial alpha 1 -adrenergic receptors is mediated by a signal transduction mechanism associated with Gs protein. The results strongly support the presence of various receptor-controlled adrenergic regulatory mechanisms on human cerebromicrovascular endothelium.
Metab Brain Dis 1992 Sep
PMID:Adrenergic receptors coupled to adenylate cyclase in human cerebromicrovascular endothelium. 133 35

Initially we established that, in human platelets, low concentrations of HDL3 stimulate phosphatidylcholine (PC) hydrolysis and a transient increase in 1,2-diacylglycerol (DAG). In (3H) PC prelabelled platelets, phosphocholine is released into the medium during HDL3 induced PC turnover with a 1.5 to 2 fold increment, indicating that HDL3 stimulated DAG generation in platelets is likely due to phospholipase C (PLC). GTP or GTP-gamma-S augments, and pertussis toxin inhibits HDL3 stimulated DAG production. Treatment of platelet membranes with HDL3 or with proteoliposome containing apo A-I or A-II substantially prevents 41 kDa protein ADP-ribosylation that was induced by pertussis toxin, with apo A-II having an inhibitory potency greater than apo A-I. These data provide strong evidence that the pertussis sensible G protein (Go or Gi) is directly involved in coupling PLC to HDL3 receptor in platelets.
Thromb Res 1992 Sep 01
PMID:Pertussis toxin sensitive G-protein coupling of HDL receptor to phospholipase C in human platelets. 133 3


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