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 functional properties, ionic basis, and possible convergence and interaction of postsynaptic actions mediated by muscarinic and alpha 1-adrenergic receptors were examined in cat and guinea pig dorsal lateral geniculate (LGNd) neurons maintained in thalamic slices in vitro. The possible involvement of GTP-binding proteins was also examined. Extracellular recordings from cat LGNd revealed the presence of two subpopulations of neurons. The most prevalent generated rhythmic high-frequency (300-500 Hz) bursts of two to six action potentials each, with an interburst frequency of 1-3 Hz. Intracellular recordings revealed that this activity is typical of thalamocortical relay cells in the apparent absence of neuromodulatory input. Application of ACh or noradrenaline (NA) to rhythmically oscillating neurons in the cat LGNd resulted in cessation of this activity followed by the appearance of single spike firing. Intracellular recordings revealed that this change in firing mode was associated with a depolarization of the neuron out of the range of intrinsic rhythmic oscillation and into or near the single spike firing mode. The voltage characteristics of the current underlying the cholinergic and noradrenergic slow depolarization were investigated in guinea pig LGNd neurons. Application of the muscarinic agonist acetyl-beta-methylcholine (MCh) to presumed relay neurons resulted in a hyperpolarization due to the activation of an outward K+ current. This response was followed by a slow depolarization due to reduction of a relatively non-voltage-dependent potassium current distinct from IM and IAHP. Application of NA resulted in a slow depolarization that was also associated with reduction of this relatively linear K+ current. The MCh- and NA-induced slow depolarizations displayed the property of occlusion, indicating convergence of action. However, these responses were mediated by pharmacologically distinct receptors since the MCh-induced reduction in K+ current was blocked by scopolamine while that induced by NA was blocked by the alpha 1-adrenoceptor antagonist prazosin. Intracellular diffusion of GTP-gamma-S resulted in the inward current responses to NA and MCh being irreversible, suggesting the possible involvement of a G-protein. Prior exposure to pertussis toxin did not affect the inward current response to NA and MCh, while the outward K+ current responses induced by application of MCh or the GABAB agonist baclofen were blocked. These results reveal that activation of muscarinic or alpha 1-adrenergic postsynaptic receptors in the LGNd result in a shift in firing mode from rhythmic oscillation to tonic single spike activity through a decrease in a relatively linear K+ current mediated through a pertussis toxin-insensitive G-protein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus. 130 74

The selective alpha 1-adrenergic agonist methoxamine (10(-4)-10(-3) M), in the presence of propranolol (10(-6) M), can reduce both the inwardly rectifying K+ background current (IK1) and the muscarinic cholinergic receptor-activated K+ current (IK,ACh) in rabbit atrial myocytes resulting in action potential prolongation during the final phase of repolarization and a depolarization of the resting membrane potential. The reduction of these K+ currents(s) by alpha 1-adrenoceptor stimulation was insensitive to pre-treatment of atrial myocytes with pertussis toxin (0.15-0.5 micrograms/ml) and was irreversible following intracellular dialysis with the non-hydrolysable guanosine triphosphate (GTP) analogue, Gpp(NH)p (1-5 x 10(-3) M). Neither the protein kinase C (PKC) inhibitors, 1((5-isoquinolinesulphonyl)-2-methylpiperoxine (H-7) (5 x 10(-5) M) and staurosporine (1 x 10(-7) M), nor "downregulation" of PKC by prolonged phorbol ester exposure (5 x 10(-7) M, for 7-8 h) had an effect on the alpha 1-adrenergic modulation of this K+ current. Under cell-attached patch-clamp conditions, bath application of methoxamine reversibly decreased acetylcholine-induced single-channel activity, thus confirming the observed reduction of the ACh-induced current under whole-cell voltage clamp. These results demonstrate that the alpha 1-adrenoceptor, once activated, can reduce current through two different inwardly rectifying K+ channels in rabbit atrial myocytes. These current changes are mediated via a pertussis toxin-insensitive GTP-binding protein, and do not appear to involve the activation of PKC.
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PMID:Activation of alpha 1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes. 136 Oct 52

1. Endothelin is a vasoactive peptide released from vascular endothelial cells which has potent cardiac inotropic effects. We examined the effect of endothelin on the verapamil-sensitive Ca2+ current (ICa) in enzymatically dispersed rabbit ventricular myocytes. 2. Using the whole-cell voltage clamp technique with a standard dialysing pipette solution, the application of extracellular endothelin (20 nM) did not increase the peak ICa, but in fact caused a small reversible decline (903 +/- 109 pA without endothelin, 727 +/- 95 pA with endothelin (means +/- S.E.M., n = 14, P less than 0.05)). 3. If GTP (100 microM) was added to the pipette solution, the extracellular application of endothelin (0.2 or 20 nM) caused a large, reproducible increase in peak ICa (871 +/- 85 pA without endothelin, 1230 +/- 110 pA with 20 nM-endothelin (n = 10, P less than 0.05). The endothelin enhancement of ICa occurred after a delay of approximately 3-4 min at room temperature. 4. The GTP requirement for the endothelin effect on ICa suggests that its effect may be mediated through a G protein-dependent pathway. To investigate this further, experiments were performed with pipette solutions containing guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), a GDP analogue which inhibits G protein cycling. With the addition of GDP beta S (0.5-5.0 mM) to the pipette solution (along with 100 microM-GTP), the effect of endothelin on peak ICa was blocked (1062 +/- 86 pA without endothelin, 1170 +/- 134 pA with endothelin (n = 11, P greater than 0.05)). 5. Incubation of myocytes with pertussis toxin (500 ng/ml) prevented the partial ACh-induced reversal of the isoprenolol enhancement of ICa. However, this identical treatment failed to block the endothelin enhancement of the voltage-dependent Ca2+ current (n = 4). 6. Taken together, these results confirm that while the effect of endothelin in rabbit cardiac ventricular myocytes is mediated through a G protein-dependent pathway, the G protein involved is pertussis toxin-insensitive.
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PMID:Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes. 159 86

Arrival of agonist is generally thought to initiate the signal transduction process in G protein-receptor coupled systems. However, the muscarinic atrial K+ (K+[ACh]) channel opens spontaneously in the absence of applied agonist, giving a noisy appearance to the current records. We investigated the nature and origin of the noise by measuring single channel currents in cell-attached or excised, inside-out membrane patches. Guanosine triphosphate (GTP) produced identical single channel currents in a concentration- and Mg(2+)-dependent manner in the presence or absence of carbachol, but the requirements for GTP were greater in the absence of agonist. Hence the agonist-independent currents appeared to be produced by an endogenous G protein, Gk. This prediction was confirmed when an affinity-purified, sequence-specific Gi-3 alpha antibody or pertussis toxin (PTX) blocked the agonist-independent currents. Candidate endogenous agonists were ruled out by the lack of effect of their corresponding antagonists. Thus agonist-independent currents had the same nature as agonist-dependent K+[ACh] currents and seemed to originate in the same way. We have developed a hypothesis in which agonist-free, empty receptors prime Gk with GTP and Gk activates atrial K+ [ACh] channels producing basal currents or noise. Agonist-independent activation by G proteins of effectors including ion channels appears to be a common occurrence.
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PMID:The nature and origin of spontaneous noise in G protein-gated ion channels. 165 79

Using the patch clamp technique, we examined the agonist-free, basal interaction between the muscarinic acetylcholine (m-ACh) receptor and the G protein (GK)-gated muscarinic K+ channel (IK.ACh), and the modification of this interaction by ACh binding to the receptor in single atrial myocytes of guinea pig heart. In the whole cell clamp mode, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S) gradually increased the IK.ACh current in the absence of agonists (e.g., acetylcholine). This increase was inhibited in cells that were pretreated with islet-activating protein (IAP, pertussis toxin) or N-ethylmaleimide (NEM). In inside-out patches, even in the absence of agonists, intracellular GTP caused openings of IK.ACh in a concentration-dependent manner in approximately 80% of the patches. Channel activation by GTP in the absence of agonist was much less than that caused by GTP-gamma S. The agonist-independent, GTP-induced activation of IK.ACh was inhibited by the A promoter of IAP (with nicotinamide adenine dinucleotide) or NEM. As the ACh concentration was increased, the GTP-induced maximal open probability of IK.ACh was increased and the GTP concentration for the half-maximal activation of IK.ACh was decreased. Intracellular GDP inhibited the GTP-induced openings of IK.ACh in a concentration-dependent fashion. The half-inhibition of IK.ACh openings occurred at a much lower concentration of GDP in the absence of agonists than in the presence of ACh. From these results, we concluded (a) that the interaction between the m-ACh receptor and GK is essential for basal stimulation of IK.ACh, and (b) that ACh binding to the receptor accelerates the turnover of GK and increases GK's affinity to GTP analogues over GDP.
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PMID:On the mechanism of basal and agonist-induced activation of the G protein-gated muscarinic K+ channel in atrial myocytes of guinea pig heart. 168 6

Acetylcholine (ACh) depolarizes the membrane of mammalian intestinal myocytes by activating a nonselective cation channel (G. D. Benham, T. B. Bolton, and R. J. Lang. Nature Lond. 316: 345-347, 1985; R. Inoue, K. Kitamura, and H. Kuriyama. Pfluegers Arch. 410: 69-74, 1987). Here, we present evidence that occupation of the muscarinic receptor by ACh couples to channel activation via a G protein; the coupling can be blocked by pertussis toxin or by intracellular guanosine 5'-O-(2-thio-diphosphate) (GDP beta S), whereas intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) activates the channel in the absence of ACh. The currents, activated by either ACh or GTP gamma S, are nonadditive, conduct sodium ions, and are similar in their voltage dependence and facilitation by submicromolar calcium ions in the cytosol.
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PMID:Acetylcholine activates nonselective cation channels in guinea pig ileum through a G protein. 169 99

Brown-Norway rats (male) were sensitized with both dinitrophenylated-bovine serum albumin (DNP-BSA) and Bordetella pertussis simultaneously in order to induce airway hyperresponsiveness (AHR) as the first sensitization. At five days, DNP-BSA was inhaled as a booster into the airways under thiopental anaesthesia. At eight days, inhalation of antigen markedly increased the tracheal pressure (TP) in sensitized rats (11.9 +/- 1.6 cmH2O) and slightly increased TP in non-sensitized rats (1.1 +/- 0.4), the difference between the two groups being significant (p less than 0.001). Twenty-four hours after antigen challenge, the airway responsiveness to ACh in sensitized rats was markedly increased to about 4-fold as compared to that in non-sensitized rats. Inhalation of dinitrophenylated-ovalbumin failed to increase the airway responsiveness to ACh in rats sensitized with DNP-BSA, although a marked increase in TP was induced immediately after antigen challenge. We thus succeeded in preparing a model of AHR by employing a new procedure of sensitization.
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PMID:Induction of airway hyperresponsiveness in allergic rats. 171 32

Acetylcholine (ACh) can inhibit calcium currents (ICa) in nerve cells by activating muscarinic ACh receptors (mAChR). There are several different genetic subtypes of mAChR. It is not known which subtype(s) are responsible for ICa inhibition. To resolve this issue, we measured ICa inhibition by ACh with patch-clamp recording, by using Ba2+ as charge carrier, in clones of NG108-15 neuroblastoma x glioma hybrid cells transfected with DNA for mAChRI, II, III and IV. Control (non-transfected) cells showed a mean maximum inhibition of peak ICa of 12.8 +/- 1.8% (n = 36) at 1 mM ACh. No consistent increase in inhibition was detected in vector-transfected cells, or in cells transformed to express mAChRI or mAChRIII. In contrast, inhibition was significantly increased in clones transformed to express mAChRII or mAChRIV. Inhibition was not correlated with the number of muscarinic receptors as determined by 3H-quinuclidinyl benzilate binding. Inhibition in both control and transfected cells was prevented by pretreatment with pertussis toxin (PTx). Inhibition persisted in the presence of extracellular or intracellular dibutyryl cyclic AMP, and hence is not because of inhibition of adenylate cyclase. We conclude that the inhibition of neuronal ICa is mediated preferentially by mAChRII and mAChRIV, via a PTx-sensitive GTP-binding protein.
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PMID:Selective coupling of different muscarinic acetylcholine receptors to neuronal calcium currents in DNA-transfected cells. 198 Jul 42

Acetylcholine (ACh) hyperpolarizes adult canine Purkinje fibers and induces a decrease in their automaticity. In Purkinje fibers from young dogs, there is a biphasic effect on automaticity, which increases at low and decreases at high ACh concentrations. We used standard microelectrode techniques to study these actions of ACh. In fibers from young dogs, 10(-10) to 10(-9) M ACh increased automaticity and 10(-5) M ACh decreased automaticity. The decrease was blocked by the M2 muscarinic blocker AFDX-116, whereas the increase was blocked by the predominant M1 blocker pirenzepine. The M2 agonist oxotremorine never increased automaticity. Rather, it decreased automaticity and hyperpolarized adult and young fibers, the former more than the latter. The hyperpolarization and biphasic effect on automaticity of ACh in fibers from young dogs failed to occur after treatment with pertussis toxin, suggesting that these effects are dependent on a pertussis toxin-sensitive G protein. These electrophysiologic studies suggest that postsynaptic M1 and M2 muscarinic processes modulate the automatic response of Purkinje fibers from young dogs and that the postsynaptic M1 pathway is no longer seen in the adult.
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PMID:Developmental changes in the muscarinic stimulation of canine Purkinje fibers. 211 80

1. The LTC4 synthase activity is rich in the microsomal fraction of the guinea pig spleen and lung. The enzyme was partially purified from the guinea pig lung and separated from the microsomal glutathione S-transferase (GST), by column chromatograpy. The enzyme has a specific activity of 40 nmol/min.mg, and acts preferentially on 5, 6-LTA4. Various types of cytosolic GSTs utilize all types of LTA4 isomers (5,6-, 11,12- and 14,15-LTA4) almost to the same extent, and methyl ester forms are better substrates for GST. 2. Two different types of GSTs (Yn1n1 and P) were purified from rat brain cytosol, to homogeneity. Because both types have a high LTC4 synthase activity, they may participate in the LTC4 production in the rat brain. 3. LTC4, produced in the guinea pig atrium, stimulates pertussis toxin (IAP)-sensitive muscarinic K+ channel (IK.ACh). The negative chronotropic action of alpha 1-adrenergic agonist might relate to the production of arachidonate lipoxygenase metabolites. These results together with the findings in Aplysia sensory neurons, suggest a novel mode of eicosanoid actions.
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PMID:Biosynthesis and functions of leukotriene C4. 214


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