UMLS:C0043167 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for phospholipase C (PLC) hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) as a mechanism of alpha 1-adrenergic signal transduction in human airway epithelial cells (AEC) was investigated in isolated normal tracheal and cystic fibrosis (CF) nasal epithelial cells grown in in vitro culture and prelabeled with 3 muCi myo-[3H]inositol/ml for 72 h. Breakdown of polyphosphoinositides was measured using thin-layer chromatography to detect phosphatidylinositol, phosphatidylinositol 4-phosphate (PIP), and PIP2. Inositol phosphates were separated by ion-exchange column chromatography. In normal AEC, the addition of the endogenous catecholamine l-epinephrine produced a rapid, transient accumulation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate (IP2) and breakdown of PIP and PIP2. IP3 increased 1.7-fold and IP2 1.6-fold after 20 and 40 s, respectively. A maximal decrease of 35% PIP2 and 30% PIP is observed after 20 and 40 s, respectively. The effects of l-epinephrine were not blocked by the beta-adrenergic antagonist dl-propranolol but were mimicked by the alpha 1-adrenergic agonist methoxamine. Prazosin, an alpha 1-adrenergic antagonist, and pertussis toxin (PTX) blocked the effects of l-epinephrine and methoxamine. Addition of l-epinephrine and methoxamine to CF nasal epithelial cells also induced prazosin-sensitive polyphosphoinositide breakdown and inositol phosphate accumulation. A 2.2-fold accumulation of IP3 was observed after 10 s and 2.0-fold increase in IP2 after 20 s. Maximal decreases of 32% PIP2 and 23% PIP levels were observed after 20-s incubation with l-epinephrine. PTX reduced the effects of l-epinephrine and significantly blocked the effects of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Alpha 1-adrenergic signaling in human airway epithelial cells involves inositol lipid and phosphate metabolism. 134

1. The effects of selective alpha 1- and alpha 2-adrenoceptor agonists and antagonists on the stimulation-induced (S-I) outflow of radioactivity at 2 Hz were investigated in superfused rabbit renal arteries incubated with [3H]-noradrenaline. 2. The alpha 1-adrenoceptor agonist methoxamine (10 microM) inhibited S-I outflow of radioactivity and this effect was abolished by the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) but not by the alpha 2-adrenoceptor antagonist rauwolscine (1 microM). Neither the prostaglandin synthesis inhibitor indomethacin (10 microM) nor the adenosine receptor antagonist 8-phenyl-theophylline (1 microM) prevented the inhibitory effect of methoxamine. 3. The alpha 2-adrenoceptor agonists clonidine (0.1 microM) and UK 14304 (0.1 microM) both inhibited S-I outflow of radioactivity. The inhibitory effect of clonidine was blocked by rauwolscine but not by prazosin. The inhibitory effect of UK 14304 was markedly reduced by rauwolscine. 4. Prazosin (0.1 microM) alone did not enhance the S-I outflow of radioactivity at 2 Hz and slightly enhanced S-I outflow at 4 Hz. Rauwolscine (1 microM) alone markedly enhanced S-I outflow of radioactivity at 2 and 4 Hz. 5. Pretreatment of the arteries with pertussis toxin (1 microgram ml-1) did not significantly alter the inhibitory effects of methoxamine or UK 14304 or the potentiation by rauwolscine. However, pretreatment of the arteries with a higher concentration of pertussis toxin (5 micrograms ml-1) prevented the inhibitory effect of methoxamine but still did not affect the responses to UK 14304 and rauwolscine. 6. Pretreatment of the arteries with N-ethylmaleimide (NEM, 10 microM) for 30 min did not alter the inhibitory effect of methoxamine but markedly attenuated the inhibitory effect of UK 14304 and the facilitatory effect of rauwolscine. 7. The results suggest that both alpha 1- and alpha 2-adrenoceptors take part in the modulation of noradrenaline release from sympathetic nerves in rabbit renal arteries. Alpha 1-adrenoceptor mediated inhibition may be coupled to G-proteins which are pertussis toxin sensitive and alpha 2-adrenoceptor mediated inhibition to G-proteins which are NEM-sensitive.
...
PMID:Activation of alpha 1- and alpha 2-adrenoceptors inhibits noradrenaline release in rabbit renal arteries: effects of pertussis toxin and N-ethylmaleimide. 134 90

We have previously reported that the response of cultured chick cerebellar neurons to glutamate is enhanced by noradrenaline (NA) or isoproterenol and suppressed by clonidine. The present study was carried out to further specify the adrenergic receptor subtypes involved in the facilitatory effect of NA or isoproterenol and the suppressive effect of clonidine, and to examine the intracellular mechanisms underlying these modulatory effects of NA. The clonidine effect, which was mimicked by NA iontophoresed with large ejecting currents, was blocked by yohimbine and tolazoline (alpha 2 antagonists) and also by dibutyryl cyclic AMP or forskolin which augmented the glutamate response by itself. Prazosin, an alpha 1 receptor antagonist did not block the clonidine effect. NA- or isoproterenol-induced facilitation, which was mimicked by denopamine (beta 1 agonist), was antagonized by acebutolol (beta 1 antagonist) and not by ICI 118,551 (beta 2 antagonist). Pretreatment of neurons with pertussis toxin for more than 24 h blocked the suppressive action of clonidine without affecting the facilitatory action of isoproterenol. Furthermore, intracellular injection of GDP beta S inhibited the modulatory effects of either clonidine or isoproterenol. These results indicate that the facilitatory and inhibitory modulatory effects of NA may be mediated by beta 1 and alpha 2 receptors linked to cAMP systems, respectively, and the former is coupled with the stimulatory G protein (Gs) and the latter is with the inhibitory G protein (Gi).
...
PMID:Subtypes of adrenergic receptors and intracellular mechanisms involved in modulatory effects of noradrenaline on glutamate. 167 79

1. In chicken hepatocytes, alpha 1-adrenoceptor activation increased: (a) phosphatidylinositol labeling; (b) production of inositol trisphosphate; (c) cytosol calcium; and (d) phosphorylase activity. 2. Prazosin (Ki approximately 0.2-0.4 nM) was more potent in inhibiting these actions than 5-methyl-urapidil (Ki approximately 30-60 nM); these actions were sensitive to chlorethylclonidine suggesting the involvement of alpha 1B-adrenoceptors. 3. The stimulation of phosphoinositide turnover was insensitive to pertussis toxin. 4. In chicken liver membranes, [3H]prazosin binding sites (Bmax 872 fmol/mg protein) with high affinity for prazosin (KD 0.3 nM; Ki 0.4 nM) and lower affinity for 5-methyl-urapidil (Ki 46 nM) were detected, consistent with the presence of alpha 1B-adrenoceptors.
...
PMID:Characterization of the alpha 1B-adrenergic receptors of chicken hepatocytes. Signal transduction and actions. 790 11

The alpha 1- and alpha 2-adrenoceptor-stimulated contractile responses of rat tail artery rings were compared in Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were untreated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an alpha 2-adrenoceptor agonist) and cirazoline (a selective alpha 1-adrenoceptor agonist) were significantly greater in SHR than in SD or WKY, and the tissues were more sensitive to the agonists in SHR or SD than in WKY. Yohimbine (0.1 microM), a selective alpha 2-adrenoceptor antagonist, shifted the dose-response curves for clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 microM), a selective alpha 1-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were not different among these three strains of rats. Nifedipine (0.05 microM) completely blocked the response to clonidine in SD and WKY; however, in SHR, approximately one-third of the response to clonidine was resistant to nifedipine. Nifedipine, at 0.05 microM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 micrograms/kg, 3 days before experiment) almost completely blocked the responses to clonidine, but only partially inhibited those to cirazoline. After pertussis toxin pretreatment, the responses (maximal effects and EC50s) to clonidine and cirazoline were not significantly different in arteries from the three strains of rats.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of pertussis and cholera toxins on alpha-adrenoceptor function in rat tail artery: differences in hypertension. 790 52

alpha-Adrenergic receptor stimulation regulates the activity of a number of different cardiac ion channels, including those underlying one or more distinct Cl- conductances. The whole-cell patch-clamp technique was used in the present study to investigate the effects of alpha-adrenergic stimulation on the beta-adrenergically regulated Cl- current in guinea pig ventricular myocytes. Neither alpha 1-adrenergic receptor stimulation with methoxamine (25 to 500 mumol/L) nor direct activation of endogenous protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu, 100 nmol/L) evoked a Cl- current. On the contrary, the Cl- current activated by 30 nmol/L isoproterenol was inhibited by methoxamine, with an EC50 of 6.7 +/- 2.6 mumol/L, and this response was blocked by prazosin, an alpha 1-adrenergic receptor antagonist. Prazosin also decreased the EC50 for current activation by norepinephrine from 53 +/- 7.1 to 18 +/- 3.8 nmol/L, demonstrating that the ability of this endogenous neurotransmitter to activate the Cl- current through beta-adrenergic receptor stimulation is limited by its intrinsic ability to also activate alpha-adrenergic receptors. Methoxamine did not inhibit the Cl- current evoked by either direct activation of adenylate cyclase with forskolin or inhibition of phosphodiesterase activity with 3-isobutyl-1-methylxanthine, indicating that alpha-adrenergic stimulation inhibits beta-adrenergic responses at a point upstream of adenylate cyclase activation. Methoxamine also did not inhibit the Cl- current activated by histamine, suggesting that alpha-adrenergic stimulation specifically inhibits beta-adrenergic receptor-mediated responses. The inhibitory effect of methoxamine was not mimicked by PDBu, and it persisted in the presence of bisindolylmaleimide, a selective PKC inhibitor. However, methoxamine inhibition of the isoproterenol-activated Cl- current was sensitive to pertussis toxin. These results suggest that alpha-adrenergic receptor stimulation inhibits the beta-adrenergically activated Cl- current, demonstrating a novel mechanism by which alpha-adrenergic receptors may regulate ion channel activity in the heart.
...
PMID:Alpha 1-adrenergic inhibition of the beta-adrenergically activated Cl- current in guinea pig ventricular myocytes. 863 40

The aim of this study was to determine the effect of protein kinase C (PKC) activation on intracellular Ca(2+) transient and its relation to alpha(1)-adrenoceptor (alpha(1)-AR)-stimulated negative inotropic response in rat ventricles. The electromechanical responses to phenylephrine (PE) in rat ventricular muscles were concomitantly examined using the conventional microelectrode method. The responses of intracellular Ca(2+) transient and cell contractions to PE in the absence of certain pharmacological interventions were ascertained in fura-2-loaded myocytes. The influence of PE on L-type Ca(2+) current (I(Ca,L)) was also examined using a voltage clamp in a whole-cell configuration. PE did not alter the action potential parameters during the negative inotropic phase. The negative inotropic effect (NIE) was inhibited by prazosin, chloroethylclonidine (CEC) and staurosporine, but was insensitive to pertussis toxin. Desensitization of PKC after prolonged pretreatment of rat ventricles with PDBu also abolished the NIE of PE. Caffeine modulated the NIE, but thapsigargin did not. The evoked intracellular Ca(2+) transient and cell contraction were initially decreased by PE, while I(Ca,L) was not altered. Prazosin and staurosporine significantly inhibited the responses. Our data indicated that alpha(1)AR-mediated NIE in rat ventricular muscles was due to the decrease of intracellular Ca(2+) transients by the modulation of PKC on Ca(2+)-releasing channels signaling through a CEC-sensitive alpha(1)AR subtype.
...
PMID:Role of protein kinase C in mediating alpha-1-adrenoceptor-induced negative inotropic response in rat ventricles. 1097 Nov 36

The two portions of rat vas deferens differed in the postjunctional sensitivity to noradrenaline. Alpha1-adrenoceptor-linked phosphoinositide breakdown was analysed in this tissue. The noradrenaline-induced [3H]inositol phosphate accumulation was similar in both ends although the pEC50 was higher in the epididymal (5.97+/-0.07) than in the prostatic (5.47+/-0.15, P<0.01) portion. [3H]Prazosin showed similar density of binding sites in both portions. Tissue pretreated with pertussis toxin did not change [3H]inositol phosphate accumulation. Finally, Western blot analysis indicated a smaller concentration of Gq/11 protein in the prostatic half (-29+/-5%, P<0.01). These results suggest that the different sensitivity to noradrenaline could be due to the higher availability of this sort of G protein in the epididymal portion.
...
PMID:Different alpha1-adrenoceptor-induced inositol phosphate formation in the two portions of rat vas deferens. 1119 28

We showed, in rat de-endothelialised tail artery, that pertussis toxin (PTX) (1 microg/mL, 2 hr) attenuated norepinephrine (NE)-induced vasoconstriction without modifying intracellular calcium concentration [Ca2+](i) mobilisation. We suggested the existence of two NE-induced intracellular pathways: a first, which would be insensitive to PTX and lead to [Ca2+](i) mobilisation, and a second sensitive to PTX and involved in the [Ca2+](i) sensitivity of NE-induced contraction. The aim of this study was to demonstrate the existence of the second intracellular pathway. PTX-sensitive G(i/o)-proteins in rat tail artery SMC membrane were identified by immunoblot and ADP-ribosylation. [(32)P]ADP-ribosylation of alpha(i/o)-subunits was demonstrated in situ by perfusing rat de-endothelialised tail artery segments with PTX (1 microg/mL, 2 hr), which suggested that G(i/o)-protein inactivation was involved in the reduction by PTX of the [Ca2+](i) sensitivity of NE-induced contraction. Coupling between G(i/o)-proteins and NE receptors was confirmed by the NE-induced increase in G(i/o)-specific GTPase activity (24.1 +/- 1.9 vs 8.8 +/- 0.4 pmol P(i)/mg protein at 5 min; P < 0.05 vs basal). [(3)H]Prazosin-binding data showed the presence of a heterogeneous alpha(1)-AR population in rat tail artery smooth muscle cells. We demonstrated the in vitro coupling between alpha(1A)-AR subtype and alpha(i)-subunits. In conclusion, we identified, in rat de-endothelialised tail artery, a PTX-sensitive G(i/o)-protein-modulated pathway that is coupled to NE receptors via alpha(1A)-AR. We suggest that NE stimulates two alpha(1)-AR-mediated intracellular pathways: a first, which is mediated by a G(q)-protein and leads to [Ca2+](i) mobilisation and contraction, and a second, which is mediated by a G(i)-protein and is involved in the amplification of the [Ca2+](i) sensitivity of NE-induced tension.
...
PMID:Role of G(i)-proteins in norepinephrine-mediated vasoconstriction in rat tail artery smooth muscle. 1130 Oct 51

1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice. We also studied a negative inotropic effect of (-)-adrenaline. 2. Sinoatrial tachycardia, evoked by (-)-adrenaline was resistant to blockade by beta(2)-selective ICI 118,551 (50 nM) but antagonized by beta(1)-selective CGP 20712A (300 nM). This pattern was unaffected by pretreatment with pertussis toxin (PTX, 600 microg kg(-1) i.p. 24 h) which reversed carbachol-evoked bradycardia to tachycardia. 3. Increases of ventricular force by (-)-adrenaline and (-)-noradrenaline were not blocked by ICI 118,551 but antagonized by CGP 20712A. 4. Under blockade of beta-adrenoceptors, (-)-adrenaline and (-)-noradrenaline depressed ventricular force (-logIC(50)M=7.7 and 6.9). The cardiodepressant effects of (-)-adrenaline were antagonized by phentolamine (1 microM) and prazosin (1 microM) but not by (-)-bupranolol (1 microM). Prazosin potentiated the positive inotropic effects of (-)-adrenaline (in the absence of beta-blockers) from -logEC(50)M=6.2 - 6.8. 5. PTX-treatment reduced carbachol-evoked depression of ventricular force in the presence of high catecholamine concentrations. Inhibition of ventricular function of G(i) protein was verified by 82% reduction of in vitro ADP-ribosylation. PTX-treatment tended to increase the positive inotropic potency of (-)-adrenaline under all conditions investigated, including the presence of ICI 118,551. 6. (-)-Adrenaline causes murine cardiostimulation through beta(1)-adrenoceptors but not through beta(2)-adrenoceptors. The negative inotropic effects of (-)-adrenaline are mediated through ventricular alpha(1)-adrenoceptors but not through beta(3)-adrenoceptors. Both G(i) protein and alpha(1)-adrenoceptors restrain (-)-adrenaline-evoked increases in right ventricular force mediated through beta(1)-adrenoceptors.
...
PMID:Physiological antagonism between ventricular beta 1-adrenoceptors and alpha 1-adrenoceptors but no evidence for beta 2- and beta 3-adrenoceptor function in murine heart. 1201 Jul 70

1