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)

1. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 microM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by omega-conotoxin (100 nM), and unaffected by Bay K 8644 (0.1-10 microM) and nifedipine (1 microM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 microM for noradrenaline, 4 nM for somatostatin and 1 microM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current within 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were alpha 2-adrenoceptors and delta-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (Go or Gi) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.
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PMID:Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones. 198 21

1. Intracellular recordings were made from submucosal neurones of the guinea-pig ileum. The actions of noradrenaline, somatostatin and [Met5]enkephalin on nicotinic synaptic potentials (EPSPs) were studied. 2. In one series of experiments, agonists were applied by superfusion; noradrenaline (0.1-20 microM) decreased EPSP amplitude by 95-100% in all neurones. Similar application of somatostatin (1-100 nM) inhibited EPSPs in about half the neurones by a maximum of 40%. [Met5]enkephalin (0.1-10 microM) did not alter EPSPs. Idazoxan and yohimbine competitively antagonized the action of noradrenaline with dissociation equilibrium constants of 20 and 30 nM respectively. 3. In another series of experiments, noradrenaline and somatostatin were applied locally from a pipette so that they reached presynaptic terminals but not the cell bodies or axons of the presynaptic cell: noradrenaline inhibited EPSPs by 90% in all neurones but somatostatin had no effect. When applied locally to the cell bodies giving rise to the presynaptic fibres, both agonists inhibited EPSPs in half the neurones by 40%. 4. When noradrenaline was applied locally to presynaptic terminals, the latency to onset of noradrenaline to inhibit EPSPs was 45-160 ms; cadmium applied similarly depressed EPSPs in 5-50 ms. 5. Pertussis toxin pre-treatment only partially blocked presynaptic inhibition caused by noradrenaline but abolished the reduction of EPSP amplitude by somatostatin. 6. It is concluded that noradrenaline and somatostatin reduce the amplitude of the fast EPSP because they hyperpolarize cell bodies and prevent action potential initiation. Noradrenaline, but not somatostatin, has an additional action to inhibit acetylcholine release by acting at nerve terminal receptors. 7. The presynaptic inhibitory action of noradrenaline results from activation of alpha 2-adrenoceptors at nerve terminals but the mechanism(s) by which these presynaptic receptors act cannot be explained adequately by either activation of a potassium conductance and/or inhibition of a calcium conductance.
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PMID:Mechanisms underlying presynaptic inhibition through alpha 2-adrenoceptors in guinea-pig submucosal neurones. 198 22

1. Intracellular recordings were obtained from submucous plexus neurones of the guinea-pig caecum. 2. The resting membrane conductance displayed two types of inward rectification: one which developed at potentials more negative than -70 mV, and another that occurred at potentials more negative than the potassium equilibrium potential. The former inward rectification was blocked by extracellular caesium (Cs+; 1-2 mM) and the latter was blocked by Cs+ (1-2 mM) or barium (Ba2+; 30-100 microM). 3. The noradrenaline-induced current measured by subtraction of the current-voltage (I-V) relation before and after adding the agonist also showed an inward rectification around the resting potential. Ba2+ (30-100 microM) blocked both the outward and inward current induced by noradrenaline. The noradrenaline current was not affected by Cs+ (1-2 mM). Both the slow IPSP and the slow IPSC (inhibitory postsynaptic current) were reduced by Ba2+, but not by Cs+. 4. During the intracellular injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), multiple repetitive stimulation or repeated applications of noradrenaline produced irreversible membrane hyperpolarizations with a decreased membrane input resistance, until the membrane had approached the potassium equilibrium potential. 5. Pertussis toxin (1-40 micrograms/ml) abolished both the slow IPSP and the noradrenaline hyperpolarization without affecting the nicotinic fast EPSP or the slow EPSP. 6. Superfusion with a Ca(2+)-free, high-Mg2+ (12 mM) solution caused a membrane depolarization associated with an increased input resistance. It eliminated the Ca2+ spikes, the slow after-hyperpolarizations following the spikes, and the synaptic potentials within 3 min. Prolonged exposure (longer than 20 min) to this solution resulted in a progressive decline of the noradrenaline hyperpolarization. 7. Intracellular injection of ethylene glycol-bis(beta-aminoethylether)N,N,N',N'-tetraacetic acid (EGTA) reduced the slow IPSP and the noradrenaline hyperpolarization. Superfusion with a membrane-permeable Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA/AM; 10-200 microM) reduced the noradrenaline hyperpolarization. 8. Procaine reversibly reduced the slow IPSP and noradrenaline hyperpolarization without affecting the fast EPSP or slow EPSP at concentrations up to 300 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms underlying intracellular signal transduction of the slow IPSP in submucous neurones of the guinea-pig caecum. 206 48

Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells.
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PMID:Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. 210 80

1. The adenosine receptor (P1-purinoceptor) agonists N6-cyclopentyladenosine and N-5'-ethyl-carboxamidoadenosine at concentrations up to 10 mumols 1(-1) affected neither basal, nor noradrenaline- and angiotensin II-stimulated formation of inositol-1-phosphate, inositol-1,4-bisphosphate, and inositol-1,4,5-trisphosphate in slices of rat renal cortex. 2. In contrast, adenine nucleotides (P2-purinoceptor agonists) markedly stimulated inositol phosphate formation. The observed rank order of potency adenosine-5'-O-(2-thiodiphosphate) (EC50 39 mumols 1(-1] greater than adenosine-5'-O-(3-thiotriphosphate) (587) greater than or equal to 5'-adenylylimidodiphosphate (App(NH)p, 899) greater than adenylyl-(beta, gamma-methylene)-diphosphate (4,181) was consistent with the interaction of the compounds with the P2Y-subtype of P2-purinoceptors. AMP and the ADP analogue (alpha, beta-methylene)-adenosine-5'-diphosphate were ineffective. ATP and ADP (less than or equal to 10 mmol 1(-1] did not produce a consistent increase, owing to their hydrolytic degradation in the incubation medium. 3. Whereas the inositol phosphate response to App(NH)p was linear only up to 5 min incubation, the time-dependent stimulation of noradrenaline declined at a slower rate. Following pre-exposure of the renal cortical slices to App(NH)p, renewed addition of App(NH)p caused no further enhancement in the accumulation of inositol phosphates, whilst noradrenaline was still capable of eliciting a response. This suggests that the apparent loss of responsiveness to App(NH)p is not due to substrate depletion or enzymatic inactivation, but most likely attributable to homologous desensitization of the purinoceptor. 4. Pretreatment of the animals with pertussis toxin caused a substantial reduction of functional Gi-protein, as indicated by the lack of [32P]-NAD incorporation in a membrane preparation of the renal cortex. Nevertheless, the increase in inositol phosphate formation induced by noradrenaline, angiotensin II, and App(NH)p was not significantly impaired. 5. We conclude that P2 gamma-purinoceptors are present in the renal cortex; these receptors stimulate formation of inositol phosphates via a pertussis toxin-insensitive pathway and undergo homologous desensitization. On the other hand, our results suggest that renal A,-adenosine receptors do not use stimulation of phosphoinositide breakdown as a transmembrane signalling system.
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PMID:P2-, but not P1-purinoceptors mediate formation of 1, 4, 5-inositol trisphosphate and its metabolites via a pertussis toxin-insensitive pathway in the rat renal cortex. 211 89

Noradrenaline (NA) stimulated the release of arachidonic acid (AA) from the [3H]AA-labelled rabbit platelets via alpha 2-adrenergic receptors, since the effect of NA was inhibited by yohimbine. The stimulatory effect of NA in digitonin-permeabilized platelets was completely dependent on the simultaneous presence of GTP and Ca2+. The NA- and thrombin-stimulated releases of AA were markedly decreased by the prior ADP-ribosylation of the permeabilized platelets with pertussis toxin. Antiserum directed against the pig brain Go (a GTP-binding protein of unknown function), recognizing both alpha 39 and beta 35,36 subunits, but not alpha 41, of pig brain, reacted with 41 kDa and 40 kDa bands, with not one of 39 kDa, in rabbit platelet membranes. Anti-Go antiserum inhibited guanosine 5'-[gamma-thio]triphosphate-, A1F4(-)-, NA- and thrombin-stimulated AA releases in the membranes. Although the effect of thrombin was inhibited by low concentrations of anti-Go antiserum, high concentrations of the antiserum was needed for inhibition of the NA effect. Antiserum directed against the pig brain G1 (inhibitory G-protein), recognizing both alpha 41 and beta 35,36 subunits, but not alpha 39, of pig brain, reacted with the 41 kDa band in platelets. Anti-G1 antiserum inhibited only the effect of NA. Reconstitution of the platelet membranes ADP-ribosylated by pertussis toxin with Go, not Gi, purified from pig brain restored the thrombin-stimulated release of AA. In contrast, reconstitution of those membranes with Gi, not Go, restored the NA-stimulated release of AA. These results indicate that different GTP-binding proteins, Gi- and Go-like proteins, may be involved in the mechanism of signal transduction from alpha 2-adrenergic receptors and thrombin receptors to phospholipase A2 in rabbit platelets.
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PMID:Possible involvement of different GTP-binding proteins in noradrenaline- and thrombin-stimulated release of arachidonic acid in rabbit platelets. 211 62

5-Hydroxytryptamine (5-HT) stimulates the rate and force of cardiac contraction. However, the molecular mechanisms of 5-HT actions on the heart are unknown. We examined effects of 5-HT on phospholipase C-mediated hydrolysis of phosphoinositides and its regulation in cultured fetal mouse ventricular myocytes labeled with [3H]inositol. Accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate was assessed after stimulation with 5-HT, catecholamines, and AlF4-. Inositol bisphosphate and trisphosphate reached a peak at 15 minutes by 5-HT stimulation and at 30 minutes by AlF4- stimulation. Inositol monophosphate accumulated linearly for at least 30 minutes in the presence of LiCl. The 5-HT effect was dose dependent, and the threshold concentration was 0.1 microM with the half-maximum effective concentration of 1 microM. Ketanserin in nanomolar concentrations inhibited the phospholipase C reaction by 100 microM 5-HT with the half-maximum inhibitory concentration of 0.5 nM. Pertussis toxin (100-1,000 ng/ml) did not influence the phospholipase C reaction by 5-HT, but it partially inhibited the reaction by AlF4-. Protein kinase C-activating phorbol esters like 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13-dibutyrate, but not 4 alpha-phorbol 12,13-didecanoate, which is inactive for protein kinase C, completely inhibited the reaction by 5-HT; TPA showed 30% inhibition on the reaction by AlF4-. The magnitude of accumulated inositol phosphates by AlF4- was at least several times greater than that by 5-HT. Norepinephrine- and epinephrine-stimulated phospholipase C reactions were completely abolished by prazosin. These results suggest that 5-HT directly stimulates phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 (5-HT2) receptors in the ventricular myocytes and that this reaction is negatively regulated by protein kinase C. 5-HT2 receptors may be coupled to phospholipase C via a pertussis toxin-insensitive GTP-binding protein in the myocytes.
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PMID:5-Hydroxytryptamine induces phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 receptors in cultured fetal mouse ventricular myocytes. 216 Aug 68

In slices of rat kidney cortex incubated in [3H]noradrenaline, the alpha 1-adrenoceptor agonist methoxamine (10 microM), the alpha 2-adrenoceptor agonist clonidine (0.1 microM), as well as adenosine (10 microM), inhibited the electrical stimulation-induced (S-I) outflow of radioactivity, at a stimulation frequency of 1 Hz. Prior treatment of rats with pertussis toxin (25 micrograms/kg i.v.), which abolished the negative inotropic effect of carbachol (10 microM) on isolated atria, prevented the inhibition caused by methoxamine, but not that caused by clonidine or adenosine. At a stimulation frequency of 5 Hz, the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the prostaglandin synthesis inhibitor indomethacin (10 microM) both facilitated the S-I outflow of radioactivity, and neither of these effects were altered by pertussis toxin. These results suggest that a pertussis toxin sensitive G-protein is involved in alpha 1-adrenoceptor inhibition of noradrenaline release, but not in alpha 2-adrenoceptor, adenosine or prostaglandin inhibition.
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PMID:Pertussis toxin differentiates between alpha 1- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from rat kidney cortex. 216 56

1. We have investigated the effects of pertussis toxin treatment on a variety of peripheral tissues in the rat. 2. Incubation with pertussis toxin (1 microgram ml-1) in vitro failed to alter the negative inotropic actions of acetylcholine in rat left atria. 3. Pretreatment with pertussis toxin (6 micrograms kg-1, i.v., 3-4 days) abolished the negative inotropic actions of acetylcholine in rat left atria. 4. Pretreatment with pertussis toxin (40 micrograms kg-1, i.v., 3-4 days) failed to alter the prejunctional inhibitory actions of the alpha 2-adrenoceptor agonist xylazine, either in terms of the isometric contraction to a single stimulus in rat vas deferens or in terms of stimulation-evoked overflow of tritium in atria pre-incubated with [3H]-noradrenaline. 5. Pretreatment with pertussis toxin (6 micrograms kg-1, i.v., 3-4 days) failed to affect, and pertussis toxin (40 micrograms kg-1, i.v., 3-4 days) potentiated endothelium-dependent relaxations of rat aorta to histamine and acetylcholine. 6. It seems unlikely that peripheral prejunctional actions of alpha 2-adrenoceptor agonists or endothelium-dependent relaxations of rat aorta involve pertussis toxin-sensitive G proteins.
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PMID:No effect of pertussis toxin on peripheral prejunctional alpha 2-adrenoceptor-mediated responses and on endothelium-dependent relaxations in the rat. 216 38

Agonist-induced PIP2 breakdown has been demonstrated in permeabilized vascular smooth muscle and shown to depend on a G protein. Segments of rat tail artery were permeabilized with ATP and EGTA after prelabeling with [3H]inositol. Norepinephrine and GTP gamma S were both able to increase levels of IP, IP2 and IP3 in the segments. The effects of both norepinephrine and GTP gamma S on the segments was non-additive. Aluminum fluoride also increased inositol phosphates in intact segments and norepinephrine-stimulated increases in IP, IP2 and IP3 were insensitive to pertussis toxin.
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PMID:G protein control of inositol lipids in intact vascular smooth muscle. 216 88


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