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)

Cultured endothelium derived from three microvascular fractions of human brain was used to characterize adrenergic receptors coupled to adenylate cyclase activity. Catecholamines (norepinephrine, epinephrine) and their analogs (isoproterenol, phenylephrine, 6-fluoronorepinephrine) dose-dependently stimulated endothelial production of cAMP. Antagonists for beta 1 and beta 2 receptors (propranolol, atenolol, and butoxamine) and for alpha 1-receptors (prazosin) dose-dependently blocked cAMP formation induced by the tested adrenergic agonists. Clonidine, an alpha 2 > alpha 1-agonist, also inhibited isoproterenol-stimulated production of cAMP while yohimbine (alpha 2 > alpha 1 antagonist) augmented the norepinephrine or epinephrine-induced accumulation of cAMP. Cholera toxin-induced ADP ribosylation of the stimulatory guanine nucleotide binding protein (Gs) abolished the stimulatory effect of norepinephrine, epinephrine, phenylephrine or 6-fluoronorepinephrine on cAMP formation. ADP ribosylation of the inhibitory guanine nucleotide binding protein (Gi) by pertussis toxin had no effect on either phenylephrine- or 6-fluoronorepinephrine-induced production of cAMP while it increased the norepinephrine and epinephrine-induced accumulation of cAMP. These findings represent the first documentation of beta 1-, beta 2-, alpha 1 and alpha 2-adrenergic receptors linked to adenylate cyclase in endothelium derived from human brain microvasculature. These data also indicate that activation of endothelial alpha 1 -adrenergic receptors is mediated by a signal transduction mechanism associated with Gs protein. The results strongly support the presence of various receptor-controlled adrenergic regulatory mechanisms on human cerebromicrovascular endothelium.
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PMID:Adrenergic receptors coupled to adenylate cyclase in human cerebromicrovascular endothelium. 133 35

The most pronounced effect of norepinephrine (NE) in the olfactory bulb is disinhibition of mitral/tufted (M/T) cells. Although it has been previously proposed that the effects of NE are mediated by a direct inhibitory action on granule cells, we have demonstrated that NE could exert it effects through inhibition of excitatory synaptic transmission from M/T cells to granule cells (Trombley and Shepherd, 1992). In order to define further the mechanism underlying NE-mediated inhibition of synaptic transmission, the effects of NE on calcium channel currents were examined using whole-cell recording techniques on bulb neurons in primary culture. NE inhibited high-threshold calcium currents at concentrations that were effective in reducing synaptic transmission. Clonidine, but not isoproterenol, mimicked the effects of NE on calcium currents, suggesting that the effects were mediated through activation of presynaptic alpha-adrenergic receptors. The effects of NE on calcium currents were irreversible in the presence of internal GTP-gamma S and prevented by preincubation with pertussis toxin, results that are consistent with a G-protein-coupled mechanism. Preincubation with pertussis toxin also prevented the effects of NE on synaptic transmission, suggesting that a similar G-protein couple mechanism mediates both effects. Intracellular dialysis with staurosporin or calcium buffering with EGTA did not prevent the effects of NE, suggesting that neither protein phosphorylation nor elevated intracellular calcium were required. These results suggest that NE may inhibit synaptic transmission in the olfactory bulb by reducing calcium currents via a G-protein-coupled alpha-adrenergic receptor.
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PMID:Norepinephrine inhibits calcium currents and EPSPs via a G-protein-coupled mechanism in olfactory bulb neurons. 140 95

1. Effects of adenosine 3':5'-cyclic monophosphate (cyclic AMP)-affecting agents were compared in mesenteric and renal resistance arteries that had been isolated from 20 week old Wistar-Kyoto rats, chemically sympathectomized, stretched to their optimal diameter for mechanical performance and made to contract in response to 30 mM potassium. 2. In mesenteric resistance arteries, isoprenaline, dopamine, NaF, forskolin, isobutyl-methylxanthine, milrinone and dibutyryl-cyclic AMP induced relaxation. Clonidine induced further increases in tension that could be reduced by pertussis toxin and prazosin but not by yohimbine. Clonidine also reduced relaxant responses to isoprenaline. 3. In renal resistance arteries, isoprenaline and dopamine failed to induce relaxation. Compared to mesenteric resistance arteries, renal vessels were less sensitive to the relaxant effect of NaF, forskolin and isobutyl-methylxanthine. Relaxant responses to dibutyryl-cyclic AMP did not differ between the two resistance arteries. 4. Indirect evidence thus suggests that in mesenteric resistance arteries, adenylate cyclase is susceptible to pharmacological activation and inhibition and is functionally coupled to relaxation. The refractory nature of renal resistance arteries to the relaxant effects of isoprenaline and dopamine could be due primarily to absence of appropriate receptors and to a relatively low activity of adenylate cyclase.
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PMID:Effects of cyclic AMP-affecting agents on contractile reactivity of isolated mesenteric and renal resistance arteries of the rat. 170 6

Adenylate cyclase activity in rabbit retinal homogenates can be stimulated directly by forskolin or through a receptor-mediated mechanism by vasoactive intestinal peptide (VIP). In contrast the alpha 2-adrenoceptor agonists clonidine and UK-14,304 reduce the basal cAMP level slightly. This was more evident following application of forskolin and VIP where the decrease of cAMP caused by clonidine and UK-14,304 is dose-dependent. The alpha 2-adrenoceptor agonist response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor, isobutylmethylxanthine, suggesting the involvement of a Gi-protein. Clonidine and UK-14,304 attenuation of elevated cAMP levels can be inhibited by the alpha 2-receptor antagonist yohimbine and phentolamine but not by the specific alpha 1-receptor antagonist, prazosin. Serotonergic, cholinergic and beta-adrenergic receptor antagonists were without effect. The results demonstrate that alpha 2-adrenergic receptors in the retina exert inhibitory effects on adenylate cyclase activity mediated by an inhibitory guanine nucleotide regulating protein.
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PMID:Inhibition of cAMP production by alpha 2-adrenoceptor stimulation in rabbit retina. 171 42

Adenylate cyclase activity was examined as a measure of inhibitory guanine nucleotide binding protein (Gi) function in liver plasma membranes from rats made chemically diabetic by streptozotocin (STZ) treatment. Clonidine activation of the alpha 2 adrenergic receptor, which activates Gi, inhibited forskolin--stimulated adenylate cyclase activity in control membranes. However, there was no effect on adenylate cyclase activity in membranes from STZ diabetic animals. Also, a polyclonal antipeptide antibody was raised to a highly conserved segment of the Gi alpha 2 subunit. This antibody specifically recognizes a 41 kilodalton protein, is blocked by an excess of peptide, does not recognize the alpha-subunit of transducin, and immunoprecipitates a 41 kilodalton protein which was ADP-ribosylated by pertussis toxin. Immunoblots using this antibody detect no difference between normal and STZ diabetic animals in the level of liver plasma membrane Gi expression. Therefore, STZ-induced diabetes altered the function of Gi but had no effect on Gi expression.
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PMID:The function but not the expression of rat liver inhibitory guanine nucleotide binding protein is altered in streptozotocin-induced diabetes. 190 25

The alpha 1- and alpha 2-adrenergic venoconstriction in dorsal hand veins of normal subjects was determined by infusion of phenylephrine or clonidine. Oral administration of prazosin reduced the constriction response to phenylephrine but not to clonidine. Subjects were treated for 3 weeks in a randomized crossover design with placebo or guanadrel sulfate. Guanadrel reduced sympathetic tone (i.e., plasma norepinephrine and norepinephrine release rate), whereas venous responses to phenylephrine and clonidine were both augmented during guanadrel treatment. The effect on phenylephrine responses was primarily attributable to a decrease in the median effective concentration with a small increase in maximum response. Clonidine showed a markedly increased maximum response with a small increase in the median effective concentration. Platelet alpha 2-adrenergic receptors increased slightly but there was no change in the amount of platelet pertussis toxin substrate during guanadrel treatment. Thus reduction in sympathetic tone in normal young men results in increased venous responses to both alpha 1- and alpha 2-agonists.
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PMID:Sensitization of human alpha 1- and alpha 2-adrenergic venous responses by guanadrel sulfate. 217 46

Addition of epinephrine to cultured FRTL-5 rat thyroid cells led to a concentration-dependent reduction of TSH- and forskolin-stimulated cAMP accumulation. Clonidine, which preferentially activates the alpha 2-adrenoreceptor, had no effect on cAMP levels. The reduction of cAMP levels by epinephrine was selectively blocked by prazosin, an alpha 1-adrenoreceptor antagonist, but not by yohimbine, an alpha 2-adrenoreceptor antagonist. Pretreatment of FRTL-5 cells with pertussis toxin failed to abolish the inhibitory effect of epinephrine on cAMP accumulation. The bioactivity of the pertussis toxin preparation in this cell line was verified by its ability to ADP-ribosylate the alpha-subunit of the inhibitory guanine nucleotide regulatory protein, Ni, as well as its ability to abolish the inhibitory effect of N6-[L-2-phenylisopropyl]-adenosine on TSH-stimulated cAMP formation. The inhibitory effect of epinephrine on cAMP levels was dependent on Ca2+ and was reversed by 3-isobutyl-1-methylxanthine. Taken together, these results suggest that epinephrine reduces cAMP levels via alpha 1-adrenoreceptors. The failure of pertussis toxin to abolish this alpha-adrenergic effect is consistent with the conclusion that epinephrine-induced attenuation of cAMP accumulation occurs through activation of a Ca2+-calmodulin-sensitive phosphodiesterase and does not involve Ni or Ni-like proteins.
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PMID:Alpha 1-adrenergic regulation of TSH-stimulated cyclic AMP accumulation in rat thyroid cells. 243 27

1. Clonidine inhibited the forskolin- and MIX-induced rate of lipolysis in brown fat adipocytes isolated from interscapular brown fat of 7-day-old rats. Its effect could be prevented by the alpha 2-antagonist yohimbine. 2. Pertussis toxin prevented the above effect of clonidine, thus indicating that alpha 2-adrenoceptors are linked with adenylate cyclase via the Ni regulatory subunit. 3. Chemical sympathectomy of 5-day-old rats by 6-hydroxydopamine increased the number of low-affinity alpha 2 sites in brown fat. 4. Chronic administration of yohimbine to 2-3-week-old rats also increased the density of alpha 2-adrenoceptors in brown fat. 5. It is suggested that brown fat of infant rats possesses functional alpha 2-adrenoceptors.
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PMID:Alpha 2-adrenergic receptors in brown adipose tissue of infant rats--II. Studies on function and regulation. 244 73

Clonidine and morphine are known to produce tolerance and dependence in rat locus coeruleus (LC) neurons after chronic administration based on electrophysiological criteria. Previous studies have shown that morphine tolerance and dependence is associated with increases in levels of adenylate cyclase, pertussis toxin-mediated ADP-ribosylation of G-proteins, and cyclic AMP-dependent protein kinase in this brain region. The present study was aimed at investigating whether clonidine tolerance and dependence is also associated with alterations in these intracellular messengers. It was found that, similar to chronic morphine, chronic (2 weeks) clonidine administration, under conditions that produce electrophysiological evidence of tolerance and dependence in LC neurons, increased levels of adenylate cyclase activity and cyclic AMP-dependent protein kinase activity in this brain region, but not in several other regions studied, which included the frontal cortex, neostriatum, and dorsal raphe. However, the changes induced by chronic clonidine in the LC, at maximal doses and duration of treatment, were only approximately 50% in magnitude of those observed in response to morphine. Unlike chronic morphine, chronic clonidine produced no change in G-protein ADP-ribosylation levels in the LC. Chronic administration of a number of other drugs, namely diazepam, chloral hydrate, and dextromethorphan, which produce electrophysiological actions distinct from those of clonidine and morphine in the LC, failed to alter adenylate cyclase and cyclic AMP-dependent protein kinase in this brain region. The results indicate that increased levels of adenylate cyclase and cyclic AMP-dependent protein kinase represent common adaptations by LC neurons to chronic clonidine and morphine, and raise the possibility that such changes contribute to the development of clonidine and morphine tolerance and dependence in these neurons.
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PMID:Regulation by chronic clonidine of adenylate cyclase and cyclic AMP-dependent protein kinase in the rat locus coeruleus. 250 46

Antilipolysis induced by insulin by adenylate cyclase inhibitors was compared in isolated human fat cells when lipolysis was activated at well-defined steps in the cyclic AMP system. The latter was achieved with isoprenaline (beta-adrenoreceptor agonist), cholera toxin and pertussis toxin (acting on the GTP-sensitive coupling proteins), forskolin (stimulating the catalytic component of adenylate cyclase), enprofylline (selective phosphodiesterase inhibitor) and N6-monobutyryl-cyclic-AMP or 8-bromo cyclic-AMP (cyclic AMP analogues which are resistant or sensitive to phosphodiesterase, respectively). Clonidine (alpha 2-adrenoreceptor agonist), prostaglandin E2 and N6-(phenylisopropyl) adenosine (adenosine analogue) failed to inhibit lipolysis stimulated by cholera toxin or pertussis toxin, but were effective under all other conditions. Insulin failed to inhibit lipolysis stimulated by enprofylline or N6-monobutyryl cyclic AMP, but was effective under all other circumstances. In conclusion, insulin and adenylate cyclase inhibitors are antilipolytic in human fat cells through different mechanisms. Adenylate cyclase inhibitors act predominantly on the GTP-sensitive coupling proteins and, to a minor extent, at some yet unidentified distal step in the lipolytic machinery. As regards insulin, the major site of the antilipolytic action is phosphodiesterase.
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PMID:Antilipolytic effects of insulin and adenylate cyclase inhibitors on isolated human fat cells. 254 39


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