Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 actions of agonists at alpha 2-adrenoceptors were investigated on single cells of the submucous plexus of the guinea pig small intestine. Intracellular recordings were made from neurons in vitro, and noradrenaline and other agonists were applied by adding them to the superfusion solution. The actions of noradrenaline released from terminals of sympathetic nerves was also studied by stimulating the nerves and recording the inhibitory postsynaptic current; this current can be mimicked by brief applications of noradrenaline from a pipette tip positioned within 50 micron of the neuron. The alpha 2-adrenoceptor-bound noradrenaline with an apparent dissociation constant of 15 microM, determined by the method of partial irreversible receptor inactivation: clonidine and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304) had dissociation constants of 36 nM and 2.5 microM respectively. Noradrenaline and UK 14304 caused maximal hyperpolarizations, or outward currents; clonidine was a full agonist in only 4 of 35 cells, a partial agonist in 25 cells, and without effect in 4 cells. Clonidine acted as a competitive antagonist of noradrenaline in those cells in which it lacked agonist action; its dissociation equilibrium constant determined by Schild analysis was about 20 nM. The potassium conductance increased by the alpha 2-adrenoceptor agonists, whether they were applied exogenously or released by stimulation of presynaptic nerves, showed marked inward rectification. The neurons showed inward rectification also in the absence of agonist; both types of rectification were eliminated by rubidium (2 mM), barium (3-30 microM) and caesium (2 mM). When the recording electrodes contained the nonhydrolysable derivative of guanosine 5'-triphosphate (GTP), guanosine 5'-O-(3-thiotriphosphate, GTP-gamma-S), the effects of applied alpha 2-adrenoceptor agonists did not reverse when they were washed from the tissue, implying that GTP hydrolysis is necessary for the termination of agonist action. Pretreatment with pertussis toxin abolished the inhibitory synaptic potential (IPSP) and agonist-induced hyperpolarizations. Phorbol 12,13-dibutyrate, forskolin, cholera toxin and sodium fluoride did not affect the responses to alpha 2-adrenoceptor agonists. The synaptic hyperpolarization resulting from sympathetic nerve stimulation, or the hyperpolarization evoked by a brief (3-5 ms) application of noradrenaline, began after a latency of about 30 and 60 ms respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of synaptic inhibition by noradrenaline acting at alpha 2-adrenoceptors. 290 Nov 10

The adrenergic agonist norepinephrine is shown to stimulate endothelium to induce protein S release and degradation, leading to diminished anti-coagulant activity and to down-regulation of protein S cell surface-binding sites. Norepinephrine-induced release of intracellular protein S was blocked by the alpha 1-adrenergic antagonist prazosin (10(-7) M) but not by the alpha-adrenergic antagonist propranolol (10(-6) M) or the alpha 2-adrenergic antagonist yohimbine (10(-5) M) indicating that this response resulted from the specific interaction of norepinephrine with a class of alpha 1-adrenergic receptors not previously observed on endothelium. Attenuation of norepinephrine-induced release of protein S by pertussis toxin in association with the ADP-ribosylation of a 41,000-D membrane protein indicates that this intracellular transduction pathway involves a regulatory G protein. The observation that protein S was released from endothelium in response to maneuvers which elevate intracellular calcium or activate protein kinase C suggests that the response may be mediated via intermediates generated through the hydrolysis of phosphoinositides. Morphologic studies were consistent with a mechanism in which norepinephrine causes exocytosis of vesicles containing protein S. In addition to release of protein S, norepinephrine also induced loss of endothelial cell protein S-binding sites, thereby blocking effective activated protein C-protein S-mediated factor Va inactivation on the cell surface. Norepinephrine-mediated endothelial cell stimulation thus results in loss of intracellular protein S and suppression of cell surface-binding sites, modulating the anti-coagulant protein C pathway on the vessel wall. These studies define a new relationship between an anti-coagulant mechanism and the autonomic nervous system, and indicate a potential role for an heretofore unrecognized class of alpha 1-adrenergic receptors in the regulation of endothelial cell physiology.
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PMID:Norepinephrine down-regulates the activity of protein S on endothelial cells. 296 46

In FRTL5 rat thyroid cells, norepinephrine, by interacting with alpha 1-adrenergic receptors, stimulates inositol phosphate formation, through activation of phospholipase C, and arachidonic acid release. Recent studies have shown that GTP-binding proteins couple several types of receptors to phospholipase C activation. The present study was undertaken to determine whether GTP-binding proteins couple alpha 1-adrenergic receptors to stimulation of phospholipase C activity and arachidonic acid release. When introduced into permeabilized FRTL5 cells, guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]), which activates many GTP-binding proteins, stimulated inositol phosphate formation and arachidonic acid release. Neomycin inhibited GTP[gamma-S]-stimulated inositol phosphate formation but was without effect on GTP[gamma-S]-stimulated arachidonic acid release, suggesting that separate GTP-binding proteins mediate each process. In addition, pertussis toxin inhibited norepinephrine-stimulated arachidonic acid release but not norepinephrine-stimulated inositol phosphate formation. Norepinephrine-stimulated arachidonic acid release but not inositol phosphate formation was also inhibited by decreased extracellular calcium and by TMB-8, suggesting a role for a phospholipase A2. To confirm that arachidonic acid was released by a phospholipase A2, FRTL5 membranes were incubated with 1-acyl-2-[3H]arachidonoyl-sn-glycero-3-phosphocholine. GTP[gamma-S] slightly stimulated arachidonic acid release, whereas norepinephrine acted synergistically with GTP[gamma-S] to stimulate arachidonic acid release. The results show that phospholipase C and phospholipase A2 are activated by alpha 1-adrenergic agonists. Both phospholipases are coupled to the receptor by GTP-binding proteins. That coupled to phospholipase A2 is pertussis toxin-sensitive, whereas that coupled to phospholipase C is pertussis toxin-insensitive.
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PMID:Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells. 302 May 40

The responsiveness of lipolysis to the stimulatory agonists noradrenaline, corticotropin and glucagon and to the inhibitory agonists N6-phenylisopropyladenosine, prostaglandin E1 and nicotinic acid was investigated with rat white adipocytes incubated with a high concentration of adenosine deaminase (1 unit/ml). The cells were obtained from fed or 48 h-starved euthyroid animals or from fed or starved animals rendered hypothyroid by 4 weeks of treatment with low-iodine diet and propylthiouracil. Hypothyroidism increased sensitivity to and efficacy of all three inhibitory agonists in their opposition of noradrenaline-stimulated lipolysis. Starvation decreased sensitivity to all three inhibitory agonists when opposing basal lipolysis. Hypothyroidism decreased sensitivity to noradrenaline, glucagon and corticotropin by 37-, 4- and 4-fold respectively and decreased the maximum response to these agonists by approx. 50%, 50% and 75% respectively. Starvation reversed decreases in maximum response to these agonists in hypothyroidism. Starvation in the euthyroid state increased sensitivity to glucagon and noradrenaline, but did not alter sensitivity to corticotropin. Cells from hypothyroid rats were relatively insensitive to Bordetella pertussis toxin, which substantially increased basal lipolysis in the euthyroid state.
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PMID:Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation. 302 50

Clonidine at 1.0 microM significantly decreased 20 mM K+-evoked release of L-[3H]noradrenaline (NA) from rat cerebral cortical slices preloaded with L-[3H]NA. Inhibitory effects of clonidine, however, were not observed in slices pretreated with 20 micrograms/ml pertussis toxin, an islet-activating protein, together with NAD and adenosine triphosphate. It is suggested that the inhibitory guanine nucleotide-binding protein (Ni) could be involved in alpha 2-adrenoceptor-mediated inhibition of NA release from nerve terminals in the central nervous system.
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PMID:Suppressing effect of pertussis toxin on clonidine-induced inhibition of noradrenaline release from cerebral cortical slices of rats. 303 64

Two possible cellular pathways of catecholamines from the chromaffin vesicles of PC12 cells to the surrounding medium are explored in this study. The direct one circumventing the cytoplasm can be activated in alpha-toxin-permeabilized cells with micromolar levels of free Ca2+. Catecholamine metabolites formed in the cytoplasm (i.e., 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylethanol) are neither formed nor released from the cells under these conditions. However, when vesicular catecholamines were discharged into the cytoplasm by addition of the ionophore nigericin, such metabolites are formed and released into the medium independent of Ca2+. Both types of experiments provide direct evidence for the operation of Ca2+-induced exocytosis of dopamine and noradrenaline in permeabilized PC12 cells. The Ca2+ dependence of dopamine or noradrenaline release, as measured by the determination of the endogenous catecholamines using the high-performance liquid chromatography technique, exhibits two different phases. One is already activated below 1 microM free Ca2+ and plateaus at 1-5 microM free Ca2+, while a second occurs in the presence of larger amounts of free Ca2+ (10-100 microM). Ca2+-induced catecholamine release from the permeabilized cells can be modulated in different ways: It is enhanced by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate and the diacylglycerol 1-oleyl-2-acetylglycerol provided Mg2+/ATP is present, and it is inhibited by guanosine 5'-O-(3-thiotriphosphate). The latter effect is abolished by pretreatment of the cells with pertussis toxin but not by cholera toxin. Thus, it appears that Ca2+-induced exocytosis can be modulated via the protein kinase C system, as well as via GTP binding proteins.
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PMID:Ca2+-stimulated catecholamine release from alpha-toxin-permeabilized PC12 cells: biochemical evidence for exocytosis and its modulation by protein kinase C and G proteins. 332 8

The effect of intrathecal pretreatment with pertussis toxin on the spinal antinociceptive effect of morphine, noradrenaline and L-baclofen was examined in rats implanted with chronic indwelling cannulas. Pretreatment with 0.25-0.75 micrograms pertussis toxin for 2-7 days inhibited antinociception produced by intrathecal injection of all three agents in the tail flick test. Inhibition also occurred in the hot plate test, but was less pronounced than in the tail flick test. When doses of the three agents giving similar levels of antinociception were compared in a single group, the degree of inhibition of antinociception was comparable. Inhibition of the effect of noradrenaline was observed up to 14 days following pretreatment. The sensitivity of spinal antinociception to pertussis toxin suggests involvement of a guanine nucleotide regulatory protein in spinal actions of morphine, noradrenaline and L-baclofen. There is support in the literature for the additional involvement of adenylate cyclase in the action of morphine and noradrenaline but not of baclofen.
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PMID:Pertussis toxin inhibits antinociception produced by intrathecal injection of morphine, noradrenaline and baclofen. 335 59

The actions of angiotensin II (AngII) and noradrenaline (NA) on smooth muscle cells of the canine mesenteric artery were studied by measurement of isometric contractions recorded from muscle strips and the intracellular Ca2+ concentration monitored with quin2-fluorescence from dispersed suspensions of single cells. The Ca2+ transients provoked by the two agonists were monophasic in shape, i.e., after application of each agonist, [Ca2+]i rose immediately within 1 s and decreased to near-basal level within 5 min. The contraction induced by NA was maintained for several minutes whilst that induced by AngII was short-lasting. When NA was repetitively applied to the strip in Ca2+ -containing solution, the same amplitude of contractions was always obtained. In contrast, after initial exposure to AngII, subsequently-applied AngII generated small contractions. In Ca2+-free solution, either agonist could induce the large contraction. After initial exposure to NA or AngII in Ca2+ -free solution, subsequently-induced contractions by either agonist were reduced. The response induced by AngII was blocked by [Sar1, Ile8]-AngII and that of NA was blocked by phentolamine. Pertussis toxin inhibited contractions induced by both agonists but not those induced by caffeine and high K+. An activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA), produced a slowly-developing contraction without any change in [Ca2+]i, and this agent inhibited the contractions and Ca2+ transients induced by both agonists. These results indicate that NA and AngII each act on a specific receptor and release Ca2+ from common intracellular storage sites through production of inositol 1,4,5-trisphosphate (InsP3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of angiotensin II and noradrenaline on smooth muscle cells of the canine mesenteric artery. 368 2

Adenosine deaminase (1 unit/ml) potentiated the lipolytic action of noradrenaline in adipocytes isolated from brown adipose tissue of 1- and 6-week-old rats by decreasing the EC50 (concn. giving 50% of maximal effect) for noradrenaline by 3-4-fold. With cells from neonatal rabbit tissue, adenosine deaminase only had a small, non-significant, effect on the EC50 for noradrenaline. Lipolysis in rat brown adipocytes was inhibited by low concentrations of N6-phenylisopropyladenosine (PIA). Rabbit cells were far less sensitive to PIA. PIA, prostaglandin E1 and nicotinate all inhibited noradrenaline-stimulated respiration in rat brown adipocytes. Hypothyroidism diminished the maximum response of respiration and lipolysis to noradrenaline in rat cells and increased the EC50 for noradrenaline. Responsiveness of lipolysis to noradrenaline was particularly decreased in hypothyroidism and was partially restored by addition of adenosine deaminase. Lipolysis in cells from hypothyroid rats was more sensitive to the anti-lipolytic action of PIA. Bordetella pertussis toxin increased lipolysis in the presence of PIA, suggesting an involvement of the Ni guanine-nucleotide-binding protein in the control of brown-adipocyte metabolism.
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PMID:Effect of adenosine deaminase, N6-phenylisopropyladenosine and hypothyroidism on the responsiveness of rat brown adipocytes to noradrenaline. 380 Sep 44

Vasodepression was found ex vivo in the isolated perfused hind legs of rats, mice and guinea-pigs with paw inflammation using maximum pressure amplitude, EAm, pD2-value and intrinsic sensitivity (i.s.) as the test parameters of dose-response curves of vasopressor substances (noradrenaline, lys- and arg-vasopressin, angiotensin II, substance P, Na2-ATP). Vasodepression is strong in the anaphylactic and dextran paw edema, moderate in the carrageenin paw edema and adjuvant arthritis, but weak in the pertussis vaccine and kaolin paw edema. It is partly long-lasting, does not closely correlate with edema strength and can also be shown in the contralateral non-inflamed leg. Thus, a vasoreactivity depressing factor(s) must be liberated from the site of inflammation and reach the general circulation. Here, the method is described using the adjuvant arthritis as an example.
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PMID:Determination of reactivity of resistance blood vessels in the isolated perfused legs of animals with inflammation as exemplified in adjuvant arthritis. 396 85


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