UMLS:C0043167 - FACTA Search

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

After intravitreal injections of cholera or pertussis toxin (CTX or PTX, 0.5 -1 microgram/eye) into the albino rabbit eye, the in vitro responses of ciliary process adenylyl cyclase (AC) to isoproterenol, vasoactive intestinal peptide (VIP), and forskolin (FSK) were increased 21-40% for PTX, but for CTX-injected eyes AC responses to fluoroaluminate, VIP and FSK decreased 70-50%. The increased responses after PTX suggests that this toxin blocked an inhibitory Gi control of AC that is present in the control tissue. However, prolonged (> 24 hr) in vivo exposure to CTX appears to down-regulate the AC enzyme. In contrast to the in vivo findings, AC responsiveness was unaffected by PTX pre-treatment of membranes in vitro, while CTX pre-treatment increased basal activity (+600%), and the FSK response (+30%), but decreased responsiveness to fluoroaluminate, VIP and isoproterenol by 88-56%. Treatment of ciliary process membranes with 32P-NAD and CTX or PTX followed by SDS-PAGE autoradiography of labelled proteins gave two bands for the G-protein alpha-subunits of Gs (45, 56 kDa) and one broad band centered at 40 kDa for Gi-type subunits respectively. Western blots using specific antibodies showed the presence of Gi type I or III, but no detectable Gi type II or Go in rabbit ciliary processes. We conclude that the changes in adenylyl cyclase enzyme responses after intraocular CTX or PTX may not correlate with cAMP levels and intraocular pressure effects. However, the in vitro biochemical data on AC responses and on G-proteins provide evidence for dual regulation of ciliary process AC by activating and inhibitory G-proteins.
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PMID:Role of G-proteins in ciliary process adenylyl cyclase responses of the albino rabbit eye. 803 85

Intravitreal injections of cholera or pertussis toxin (CTX or PTX, 0.5-1 microgram/eye) decreased intraocular pressure (IOP) up to 50% in the albino rabbit eye, which lasted up to six days. Both toxins were active on G-proteins as determined by in vitro and in vivo effects on ciliary process adenylyl cyclase activity and by ADP ribosylation of G-protein alpha-subunits with 32P-NAD. However, forty-two hours after toxin injection aqueous humor proteins increased from control levels of 0.8-1.2 mg/ml to 8-25 mg/ml. Both toxins contained 1-3 parts per thousand endotoxin sufficient to cause the IOP and aqueous humor protein responses observed. We conclude that the in vivo responses to intraocular CTX or PTX obtained from commercial sources may not provide unequivocal evidence for the role(s) of G-proteins in aqueous humor dynamics, and must be interpreted with caution.
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PMID:Endotoxins in cholera and pertussis toxins interfere with in vivo responses to these agents in the albino rabbit eye. 803 92

Modulation of the neuronal omega-conotoxin GVIA-sensitive N-type voltage-dependent calcium channel (VDCC) by neurotransmitters and guanine nucleotides suggests a dynamic interaction between activated G-protein alpha subunits and the N-type VDCC. Our previous report on the purification of the N-type VDCC (McEnery, M. W., Snowman, A. M., Sharp, A. H., Adams, M. E., and Snyder, S. H. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 11095-11099), has led us to investigate a possible association of CTXR with an endogenous G alpha subunit. The addition of the G-protein activator AIF4- modulated the 125I-CTX binding characteristics of the solubilized CTXR. Further immunological analyses employing G alpha subunit-specific antibodies to monitor the cofractionation of G alpha with 125I-CTX binding activity throughout the purification procedure indicate the selective recovery of Go alpha in the purified CTXR preparation, as neither Gs alpha, Gi alpha, nor G beta gamma could be detected. Furthermore, Go alpha associated with CTXR acted as a substrate for pertussis toxin-dependent ADP-ribosylation only upon the addition of exogenous G beta gamma subunits. These results strongly indicate a high affinity complex between an activated Go alpha and CTXR maintained throughout biochemical purification of the 125I-CTX receptor.
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PMID:The association of endogenous Go alpha with the purified omega-conotoxin GVIA receptor. 827 42

1. The effect on intracellular free calcium concentration ([Ca2+]i) of simultaneous activation of receptors coupled to phospholipase C via pertussis toxin (PTX)-sensitive and -insensitive G-proteins has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. In fura-2-loaded DDT1MF-2 cells, activation of adenosine A1-receptors (which are linked to PTX-sensitive G-proteins) with a maximal concentration of N6-cyclopentyladenosine (CPA; 300 nM) increased [Ca2+]i from 121 +/- 5 nM to 254 +/- 20 nM (n = 8). These experiments were performed in the presence of extracellular Ca2+. Stimulation of histamine H1-receptors (which are linked to PTX-insensitive G-proteins) with a low concentration of histamine (1 microM) increased [Ca2+]i from 128 +/- 8 nM to 150 +/- 13 nM (n = 8). When combined, CPA (300 nM) and histamine (1 microM) synergistically raised [Ca2+]i from 134 +/- 6 nM to 607 +/- 61 nM (n = 8). 3. Removal of extracellular Ca2+ (experiments performed in Ca(2+)-free buffer containing 0.1 mM EGTA) had no effect on the synergistic interaction between CPA (300 nM) and histamine (1 microM). 4. The addition of maximal concentrations of CPA (300 nM) and histamine (100 microM) resulted in a rise in [Ca2+]i which was additive when compared to the Ca2+ responses obtained with the two agonists alone. Low (30 nM) and subthreshold (3 nM) concentrations of CPA did not alter the Ca2+ response elicited by maximal concentrations of histamine (100 microM). 5. Subthreshold concentrations of CPA (3 nM) and low concentrations of histamine (1 microM) elicited synergistic rises in [Ca2+]i. 6 Synergistic Ca2+ responses were not observed between histamine Hl- and ATP-receptors when cells were simultaneously stimulated with either 1 microM or 10 microM of each agonist.7 These data suggest that adenosine A1-receptors linked to PTX-sensitive G-protein(s) and histamine H14-receptors linked to PTX-insensitive G-proteins interact synergistically to raise [Ca2+]i. In contrast,activation of ATP-receptors which are linked to PTX-insensitive G-protein(s) do not interact synergically with histamine H1-receptors.
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PMID:Intracellular cross-talk between receptors coupled to phospholipase C via pertussis toxin-sensitive and insensitive G-proteins in DDT1MF-2 cells. 835 67

Cholera toxin (CTX; 5 micrograms/ml), but not pertussis toxin (100 ng/ml), when preincubated with pituitary cells for 18 h, enhances the percentage of cellular LH released in response to continuous or pulsatile administration of 5 x 10(-9) M GnRH. This effect occurs without increasing total (intracellular plus extracellular) LH, indicating that it is best explained by redistribution of LH from a nonreleasable to a releasable pool. This site of action is consistent with the observation that CTX-pretreated cells are also sensitized to stimulation of LH release by the Ca2+ ionophore A23187. The observations that CTX stimulates the production of cAMP in these cells and that the sensitizing action of CTX is mimicked by (Bu)2cAMP (1 mM) are consistent with the view that a CTX-stimulated guanyl nucleotide binding protein, capable of activating adenylyl cyclase, is mediating this sensitization. We used a perifused cell system to show that the movement of LH into a releasable pool is lost with the onset of homologous desensitization due to high pulse frequency or constant administration of GnRH (5 x 10(-9) M, continuous or a pulse each 15 min). Sensitization to CTX is restored by stimulation with a high concentration of GnRH (10(-6) M) or by resetting the pulse frequency to the rate measured in vivo (a pulse each 90 min). Both of these treatments also circumvent the desensitized state, restoring LH release. These results identify a novel lesion associated with the development of desensitization in the gonadotrope and support the role of a CTX-sensitive guanyl nucleotide binding protein in regulation of pituitary responsiveness to GnRH.
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PMID:A cholera toxin-sensitive guanyl nucleotide binding protein mediates the movement of pituitary luteinizing hormone into a releasable pool: loss of this event is associated with the onset of homologous desensitization to gonadotropin-releasing hormone. 838 9

1. The effect of a range of adenosine receptor agonists on intracellular free calcium concentration ([Ca2+]i) has been studied in the hamster vas deferens smooth muscle cell line DDT1MF-2. 2. Adenosine receptor agonists elicited a rapid and maintained increase in [Ca2+]i in fura-2 loaded DDT1MF-2 cells. The initial rise could be maintained in the absence of extracellular calcium, whereas the maintained or plateau phase was dependent upon the presence of extracellular calcium and appeared to be associated with calcium influx. The rank order of agonist potencies was N6-cyclopentyladenosine > 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine > adenosine. 3. The response to 2-chloroadenosine was antagonized by the antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, KD 0.14 nM) and 8-phenyltheophylline (KD 112 nM). 4. Pretreatment with the 5-lipoxygenase inhibitor AA861 (20 microM) produced only a small (14 +/- 2%) inhibition of the [Ca2+]i response elicted by N6-cyclopentyladenosine (300 nM), in nominally Ca(2+)-free buffer containing 0.1 mM EGTA. The cyclo-oxygenase inhibitor, indomethacin (2 microM) was without effect. 5. The Ca(2+)-influx associated with the plateau phase required the continued presence of agonist on the receptor. The antagonist DPCPX (100 nM) attenuated the rise in [Ca2+]i observed when extracellular Ca2+ was re-applied after the cells had been stimulated with N6-cyclopentyladenosine (CPA; 300 nM) in experiments initiated in nominally Ca(2+)-free buffer. 6. Pretreatment with pertussis toxin (200 ng ml-1 for 4 h) inhibited the CPA (100 nM) stimulated intracellular Ca2+ release and Ca2+ influx but was without effect on the response to histamine (100 microM). 7.These data suggest that adenosine A(1)-receptor activation in DDT(1)MF-2 cells stimulates release of Ca(2+) from intracellular stores and influx of extracellular Ca(2+) through Ca(2+) entry pathways in the plasma membrane which required the continued presence of agonist on the receptor.
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PMID:Adenosine A1-receptor stimulated increases in intracellular calcium in the smooth muscle cell line, DDT1MF-2. 842 18

The effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAGO), the delta opioid receptor agonist, Tyr-D-Pen-Gly-Phe-D-penicillamine (DPDPE) and the kappa-opioid receptor agonist, dynorphin A-(1-13) on the whole-cell K+ currents (IK) of cultured mouse DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells were studied. These opioid ligands all elicited dual effects. Low concentrations (< nM) usually elicited a transient increase in IK (within 1 min), followed by a sustained decrease in IK. In contrast, microM concentrations rapidly elicited a sustained increase in IK. After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained decrease in IK evoked by < nM opioid agonists no longer occurred. Low concentrations then elicited only a sustained increase in IK. On the other hand, after chronic treatment with pertussis toxin (PTX), the usual microM opioid-induced increases in IK no longer occurred and more than half of the cells responded with a sustained decrease of IK to microM as well as nM opioids. The results suggest that mu, delta and kappa opioid receptors are each coupled to K+ channels through CTX-B- and PTX-sensitive transduction systems. Both systems have similar threshold concentrations to opioids. Activation of the CTX-B-sensitive opioid receptor/transduction system resulted in a decrease in K+ conductance of the cell which is generally associated with an increase in neuronal excitability. Activation of the other system resulted in an increase in K+ conductance which will, in general, decrease neuronal excitability. The net change in the IK depends upon which effect predominates. The dominance at different opioid concentrations may depend on the relative efficacies of the coupling of these two systems to K+ channels.
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PMID:Dual regulation by mu, delta and kappa opioid receptor agonists of K+ conductance of DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells. 857 91

1. Either intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of morphine alone at the dose of 0.2 microgram slightly increased inhibition of the tail-flick response. However, combined i.t. and i.c.v. injections of morphine at the same dose increased the inhibition of the tail-flick response in a synergistic manner. 2. Cholera toxin (CTX, 0.05 to 0.5 microgram) pretreated i.t. or i.c.v. for 24 hr or pertussis toxin (PTX, 0.05 to 0.5 microgram) for 6 days dose-dependently attenuated inhibition of the tail-flick response induced by combined i.t. and i.c.v. injection of morphine. 3. 3-Isobutyl-1-methylxanthine (IBMX, 0.001 to 0.1 ng) pretreated i.t. for 10 min dose-dependently attenuated the inhibition of the tail-flick response induced by combined i.t. and i.c.v. injections of morphine. However, IBMX pretreated i.c.v. for 10 min was not effective in attenuating the inhibition of the tail-flick response induced by combined i.t. and i.c.v. injections of morphine. 4. It is concluded that both spinal and supraspinal CTX- and PTX-sensitive G-proteins are involved in the antinociception produced by morphine-induced multiplicative interaction between spinal and supraspinal sites. However, only spinal but not supraspinal cAMP phosphodiesterase is involved in mediating antinociception induced by morphine-induced multiplicative interaction.
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PMID:Multiplicative interaction between intrathecally and intracerebroventricularly administered morphine for antinociception in the mouse: effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin. 869 Feb 52

GTP-binding proteins are key elements in coupling receptors to various effector systems. Using ADP-ribosylation by cholera (CTX) and pertussis (PTX) toxins and an immunodetection technique, we investigated the G protein expression profile in smooth muscle of stem villi vessels obtained from human term placentae. In placental vascular smooth muscle, we report the presence of two CTX-protein substrates of 42 and 45 kDa recognized by Gs alpha antibodies, and three Gi alpha isoforms, substrates of PTX, identified as Gi1 alpha, Gi3 alpha (two proteins of 41 kDa) and Gi2 alpha (a 40-kDa protein). We also characterized another target of PTX, a 40-kDa Go alpha-immunoreactive protein and detected the PTX-insensitive Gq-Gi1 alpha proteins. To assess the functional significance of the G alpha proteins identified in this tissue, we measured the adenylyl cyclase activity in the presence of guanyl nucleotides alone or with increasing concentrations of vasoactive intestinal peptide (VIP), and examined whether VIP-bound sites, in the presence of GTP gamma S, promote the release of G alpha proteins from the membranes of vascular smooth muscle. At low concentrations (0.1 nM to 0.01 microM), guanyl nucleotides stimulated adenylyl cyclase activity in a dose-dependent manner, while at higher concentrations (10 microM to 1 mM) the stimulation rate of cAMP production by guanyl nucleotides decreased. In a dose-dependent manner, VIP in the presence of GTP gamma S increased adenylyl cyclase activity and specifically promoted the release of both Gs alpha isoforms. In contrast, the release of Gi1 and Gi2 alpha isoforms was not significantly increased in the presence of VIP, while GTP gamma S alone stimulated their release. Our data show physical evidence of the activation of Gs proteins by VIP-bound membrane receptors, resulting in dissociation and release of Gs alpha subunits in the soluble fraction. They assess the specific coupling of the two Gi alpha isoforms to VIP receptors in smooth muscle wall of placental stem villi vessels. It would be of interest to investigate whether changes in Gs alpha expression and/or function are associated with the placental angiogenesis process during pregnancy.
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PMID:G protein expression in human fetoplacental vascularization. Functional evidence for Gs alpha and Gi alpha subunits. 876 39

G-proteins define both the pharmacological characteristics and the signalling pathways of G-protein-coupled receptors. Melatonin receptors have been shown to belong to this class of receptors through their sensitivity to modulators of G-protein function. This study reveals that 2-125I-iodomelatonin (125I-MEL) binding to different target tissues is differentially affected by agents which disrupt the G-protein cycle. GTP gamma S, pertussis (PTX) and cholera (CTX) toxins each reduce 125I-MEL binding to ovine pars tuberalis (oPT) and lizard brain membranes, whereas chicken brain is affected only by GTP gamma S (guanosine 5'-O-(3-thiotriphosphate)) and CTX. In contrast, high affinity binding of 125I-MEL in the ovine hippocampus was not affected by any of these agents. This finding, together with the fact that neural binding sites of the sheep brain were found to have markedly lower molecular mass than those of the oPT on native gel electrophoresis (365 vs 525 kDa), suggests that the neural 125I-MEL binding sites in sheep may not be G-protein coupled. Pharmacologically, however, the binding sites in the hippocampus and oPT could not be distinguished using 11 analogues of melatonin. Therefore, these data support the notion not only of multiple forms of melatonin receptor/G-protein complex, but of high affinity binding sites for 125I-MEL which do not display sensitivity to guanine nucleotides.
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PMID:Differential regulation of melatonin receptors in sheep, chicken and lizard brains by cholera and pertussis toxins and guanine nucleotides. 881 43

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