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)

Neuropeptide Y (NPY) presynaptically inhibits excitatory transmission in area CA1 of rat hippocampus. As postsynaptic NPY receptors in certain other tissues have been shown to be coupled to G-proteins, we have tested the hypothesis that the hippocampal NPY effects are also mediated by G-proteins. Pretreatment of rats with pertussis toxin (PTX) was ineffective in blocking NPY's presynaptic inhibitory actions in area CA1 of the hippocampal slice. The presynaptic inhibitory action of baclofen was also unaffected by PTX pretreatment. However, in these same PTX-pretreated slices, the postsynaptic hyperpolarizing actions of baclofen and 5-hydroxytryptamine were blocked. We suggest that pre- and postsynaptic receptors possess different coupling mechanisms to their effectors.
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PMID:Presynaptic inhibition by neuropeptide Y and baclofen in hippocampus: insensitivity to pertussis toxin treatment. 250 90

Pretreatment of bovine aortic smooth muscle cells in culture with pertussis toxin (PT) or cholera toxin (CT) potentiated the synthesis of prostacyclin (PGI2) induced by 5-hydroxytryptamine (5-HT) and phorbol-12-myristate, 13-acetate (PMA). The production of PGI2 by explants from the bovine aortic media was also synergistically stimulated by 5-HT and CT, whereas PT was inactive. These data are consistent with the hypothesis that guanosine 5'-triphosphate binding proteins are directly involved in the control of phospholipases which release free arachidonic acid for prostaglandin synthesis.
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PMID:Cholera and pertussis toxins amplify prostacyclin synthesis in aortic smooth muscle cells. 251 91

The inhibition of forskolin-stimulated adenylate cyclase activity by 5-hydroxytryptamine (5-HT) receptor agonists was measured in rat hippocampal membranes isolated from animals treated with vehicle or islet-activating protein (IAP; pertussis toxin). In vehicle-treated animals, 5-HT, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, and gepirone were potent in inhibiting forskolin-stimulated adenylate cyclase activity with EC50 values of 60, 76, 376, and 530 nM, respectively. IAP treatment reduced by 30-55% the 5-HT1A agonist inhibition of adenylate cyclase activity via 5-HT1A receptors. The data indicate that the inhibitory guanine nucleotide-binding protein or Go (a similar GTP-binding protein of unknown function purified from brain) mediates the 5-HT1A agonist inhibition of hippocampal adenylate cyclase.
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PMID:Pertussis toxin attenuates 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes. 252 68

Serotonin has no obvious effect on basal cyclic AMP levels but reduces the forskolin-, isoproterenol-, and vasoactive intestinal peptide-induced stimulation of cyclic AMP levels in a dose-dependent manner. Serotonergic, cholinergic, muscarinic, alpha-adrenergic, and dopaminergic antagonists have no effect on the serotonin response. Topical application of a serotonin/pargyline solution to the living eye causes desensitisation of the serotonin response in the iris-ciliary body, an observation confirming the presence of specific serotonergic receptors linked to adenylate cyclase. The 5-HT1A [5-hydroxytryptamine (serotonin) type 1A] receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone mimic the serotonin response in reducing the forskolin-stimulated cyclic AMP levels, as do the indole derivatives 5-methoxytryptamine, 5-hydroxtryptophan, and tryptamine. However, the ineffectiveness of the 5-HT1A agonist ipsapirone and the inability of spiroxatrine to block the serotonin response show that classical 5-HT1A receptors are not involved. The serotonin response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor theophylline, which indicates the involvement of an inhibitory guanine regulatory protein in the coupling of the serotonin receptor to the adenylate cyclase catalytic unit.
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PMID:Evidence for the presence of serotonin receptors negatively coupled to adenylate cyclase in the rabbit iris-ciliary body. 254 97

The signal transduction pathways of the cloned human 5-HT1A receptor have been examined in two mammalian cell lines transiently (COS-7) or permanently (HeLa) expressing this receptor gene. In both systems, 5-hydroxytryptamine (5-HT, serotonin) mediated a marked inhibition of beta 2-adrenergic agonist-stimulated (80% inhibition in COS-7 cells) or forskolin-stimulated cAMP formation (up to 90% inhibition in HeLa cells). This serotonin effect (EC50 = 20 nM) could be competitively antagonized by metitepine and spiperone (Ki = 81 and 31 nM, respectively) and could also be blocked by pretreatment of cells with pertussis toxin. In both cell types, 5-HT failed to stimulate adenylyl cyclase through the expressed receptors. In HeLa cells, 5-HT also stimulated phospholipase C (approximately 40-75% stimulation of formation of inositol phosphates). Again, this effect was inhibited by metitepine. However, the EC50 of 5-HT was considerably higher (approximately 3.2 microM) than that found for inhibition of adenylyl cyclase. Both pathways were demonstrated to be similarly affected by pertussis toxin. These findings indicate that like the M2 and M3 muscarinic cholinergic receptors, the 5-HT1A receptor can couple to multiple transduction pathways with varying efficiencies via pertussis toxin-sensitive G-proteins. The lack of stimulation of cAMP formation by this 5-HT1A receptor may suggest the existence of another pharmacologically closely related receptor.
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PMID:Effector coupling mechanisms of the cloned 5-HT1A receptor. 254 39

1. Pertussis toxin inactivates Gi-protein, which mediates the inhibitory effects of receptors on adenylate cyclase. The effects of the toxin on endothelium-dependent and independent relaxations were determined in porcine coronary arteries. 2. Arterial rings (with and without endothelium) were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution (maintained at 37 degrees C, gassed with 95% O2 and 5% CO2). 3. Incubation of the tissues with pertussis toxin (100 ng/ml for 60 min) virtually abolished the endothelium-dependent relaxations produced by the alpha 2-adrenergic agonist, UK 14304, and by 5-hydroxytryptamine. Endothelium-dependent relaxations to thrombin and to aggregating platelets were markedly reduced, whereas those produced by bradykinin were only minimally affected. Endothelium-dependent responses produced by the calcium ionophore (A23187) and by adenosine diphosphate were not altered by pertussis toxin. 4. Pertussis toxin did not affect the direct, endothelium-independent relaxations produced by nitric oxide, or by adenosine diphosphate. 5. These experiments demonstrate that pertussis toxin interferes with the release of endothelium-derived relaxing factor(s) evoked by certain, but not all, endothelial activators. The release of endothelium-derived relaxing factor(s) may occur through different pathways involving Gi-protein-dependent and independent mechanisms.
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PMID:Pertussis toxin inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. 277 38

Serotonin (5-hydroxytryptamine, 5-HT) inhibited the formation of cAMP promoted by vasoactive intestinal polypeptide, plus forskolin, in mouse hippocampal and cortical neurons in primary culture. The rank order of potencies of classical 5-HT1 agonists in inhibiting cAMP formation in hippocampal neurons was 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 5-carboxamidotryptamine (5-CT) greater than d-lysergic acid diethylamide greater than 5-HT greater than 5-methoxy-N,N-dimethyltryptamine (5-MeO-N,N-DMT) greater than RU 24969 greater than ipsapirone greater than bufotenine greater than buspirone [half-maximal efficacy (EC50) = 7, 18, 30, 52, 90, 102, 100, 110, and 128 nM, respectively]. All the tryptamine derivatives substituted in position 5 of the indol were potent agonists [5-HT, 5-CT, 5-MeO-N,N-DMT, 5-methoxytryptamine, and bufotenine], whereas tryptamine, N-methyltryptamine, and N,N-dimethyltryptamine were poor agonists. The most potent antagonists tested were spiperone, (+/-)-pindolol, (+/-)-cyanopindolol, WB4101, and methiothepin, the affinity of spiperone for this receptor being 22 nM. In contrast, ketanserin, a specific 5-HT2 antagonist, and 5-HT3-selective drugs (ICS 205 930 and MDL 72222) were very weak in antagonizing the 5-HT-inhibited cAMP formation. The pharmacological profiles of 5-HT receptors mediating the inhibition of cAMP formation indicate that these receptors correspond to the 5-HT1A-binding site subtypes. Experiments with the Bordetella pertussis toxin indicate that the 5-HT1A receptor mediating inhibition of cAMP production involves a pertussis toxin-sensitive GTP-binding protein. In the absence of VIP, cAMP formation could be stimulated through a 5-HT receptor, but the specific 5-HT1A agonists, 8-OH-DPAT and RU 24969 did not stimulate cAMP production. These results suggest that in mouse embryonic hippocampal neurons, the 5-HT1A receptors, which are negatively coupled to adenylate cyclase, are distinct from the receptor positively coupled to this enzyme. The pharmacological characterization of the 5-HT receptor negatively coupled to adenylate cyclase in mouse embryonic cortical neurons indicates that it differs from the 5-HT1A receptor found in hippocampal neurons. Its main differences with the 5-HT1A receptor in hippocampal neurons are as follows: 1) 8-OH-DPAT was only a poor partial agonist in cortical neurons, whereas it was the best full agonist in hippocampal neurons; and 2) metergoline and methysergide as well as the anxiolytic drugs, ipsapirone and buspirone, which were potent agonists in hippocampal neurons, were competitive antagonists in cortical neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. 282 13

The ability of 5-hydroxytryptamine (5-HT) and the 5-HT1A selective agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to modulate adenylate cyclase activity was measured in rat hippocampus. In vitro ADP ribosylation of GTP-binding proteins by pertussis toxin in this tissue abolished both 5-HT- and 8-OH-DPAT-induced inhibition of forskolin-stimulated adenylate cyclase activity. These findings indicate that 5-HT1A receptors are linked a pertussis-sensitive Gi protein in rat hippocampus.
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PMID:5-Hydroxytryptamine1A receptors are linked to a Gi-adenylate cyclase complex in rat hippocampus. 297 52

Growth factors can be divided into two classes which act through distinct signal transduction pathways. One class including epidermal growth factor, platelet derived growth factor and fibroblast growth factor activates receptor tyrosine kinases, and the second class, including thrombin, bombesin, bradykinin and vasopressin activates a phosphoinositide-specific phospholipase C through GTP-binding proteins which can be inactivated by pertussis toxin. In Chinese hamster lung fibroblasts, thrombin-induced mitogenicity seems to correlate well with phospholipase C activation and both events are sensitive to pertussis toxin. Thrombin, like the other mitogens in this class, simultaneously inhibits adenylate cyclase. This involves an inhibitory G protein (Gi), a well established pertussis toxin substrate. The relative contributions of the two signalling pathways to mitogenicity has not been evaluated so far. We report here that the neurotransmitter serotonin (5-hydroxytryptamine), a contracting agent and mitogen for smooth muscle cells, activates phospholipase C, inhibits adenylate cyclase and stimulates DNA synthesis in fibroblasts. These events are sensitive to pertussis toxin. We show that the mitogenicity of 5-hydroxytryptamine can be uncoupled from phospholipase C activation that is mediated by 5-HT2 receptors, but correlates perfectly with inhibition of adenylate cyclase through 5-HT1B receptor. We propose that inhibition of adenylate cyclase or activation of an undefined effector system by Gi is important in 5-hydroxytryptamine induced DNA synthesis and contributes to the strong mitogenicity of the other members of this family of growth factors.
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PMID:Serotonin stimulates DNA synthesis in fibroblasts acting through 5-HT1B receptors coupled to a Gi-protein. 304 68

The liver fluke Fasciola hepatica has serotonin (5-hydroxytryptamine) receptors that function through a transmembrane signalling system requiring GTP which activates adenylate cyclase (ATP pyrophosphate-lyase (cyclising), EC 4.6.1.1). Non-hydrolysable GTP analogs and NaF activate adenylate cyclase in membrane particles of these organisms. The nature of GTP-binding proteins in these membranes was studied using bacterial toxins and photoaffinity labelling. Treatment of membrane particles from flukes with cholera toxin increased basal adenylate cyclase activity, but markedly decreased activation by serotonin, non-hydrolysable GTP analogs, and NaF. [32P]ADP-ribosylation by cholera toxin or photoaffinity labelling with [32P]-8-N3GTP identified a 53 kDa protein and a 45 kDa protein which appeared to be similar to the forms of the alpha-subunit of the GTP-binding protein associated with adenylate cyclase in mammals. Treatment of membrane particles by pertussis toxin did not significantly change basal adenylate cyclase activity and did not change the stimulation of cyclase by activators. A 43 kDa protein which was [32P]ADP-ribosylated by either cholera or pertussis toxin, depending on the conditions used, and photoaffinity labelled by [32P]-8-N3GTP may be part of the transmembrane signalling system in the liver flukes.
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PMID:GTP-binding proteins associated with serotonin-activated adenylate cyclase in Fasciola hepatica. 309 38


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