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

The cellular mechanisms underlying the inhibitory effects of phenylephrine on dihydropyridine-sensitive, voltage-dependent Ca2+ currents recorded from single smooth muscle cells dissociated from the rat anococcygeus muscle were examined. Phenylephrine (0.1-30 microM) produced a concentration-dependent inhibition of the Ca2+ current; the maximum response occurred at a concentration of 10 microM, which inhibited the peak inward current evoked at 0 mV by 57.7 +/- 4% (n = 8). The response to phenylephrine was reduced but not abolished in cells containing 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), and it persisted in cells dialysed internally with heparin (5 mg.ml-1). This was despite the fact that both EGTA (5 mM) and heparin were able to block the phenylephrine-induced, Ca(2+)-dependent chloride current recorded in the same cells. The inhibition of the Ca2+ current produced by phenylephrine was abolished in cells containing guanosine 5'-[beta-thio]diphosphate (GDP-beta-S) but persisted in cells pre-treated with pertussis toxin. Our results suggest that the inhibition of L-type Ca2+ current seen following alpha-adrenoceptor activation occurs by a mechanism independent from the inositol trisphosphate-mediated release of Ca2+ from intracellular stores.
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PMID:Inhibition of voltage-dependent Ca(2+)-current by alpha-adrenoceptor agonists in smooth muscle cells. 777 80

We studied the receptor-effector coupling mechanism responsible for alpha 1-adrenergic receptor-induced increases in abnormal automaticity (AA) occurring at low membrane potentials in "ischemic" Purkinje fibers, superfused with Tyrode's solution containing [K+]o 10 mmol/L, pH 6.8, PO2 < 25 mm Hg. To exclude beta-adrenergic actions, propranolol was added to all solutions. We derived membrane slope resistance (Rsl) from the current-voltage relation obtained with two microelectrodes for intracellular current injection and transmembrane voltage recording. We also measured the membrane time constant, Tm, to assess changes in membrane resistance (Rm). Phenylephrine effects on Rsl in simulated ischemia were studied in the absence or presence of the alpha 1-subtype blockers WB 4101 (WB) or chloroethylclonidine (CEC), both 0.1 mumol/L, and in Purkinje fibers from dogs injected with pertussis toxin (PTX) (30 micrograms/kg i.v., 60 to 72 hours before study). There were no significant differences in mean values of Rsl before phenylephrine superfusion among all groups of Purkinje fibers. Tm increased by 23% during phenylephrine 0.1 mumol/L superfusion, and Rsl increased by 11%. These two results suggest a 23% increase in Rm with no concordant change in longitudinal resistance. In the presence of CEC, phenylephrine increased Rsl by 12%. In contrast, WB blocked phenylephrine effects on Rsl (0.3%). In PTX-treated Purkinje fibers, the levels of PTX-sensitive G protein as well as phenylephrine effects on Rsl (3%) were significantly reduced. In the absence of WB and of CEC, the phenylephrine effects both on Rsl and on the incidence of AA were directly related to the level of PTX-sensitive substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptor-effector coupling pathway for alpha 1-adrenergic modulation of abnormal automaticity in 'ischemic' canine Purkinje fibers. 790 61

1. In rabbit papillary muscles, pretreatment with pertussis toxin (PTX) significantly increased the positive inotropic response to isoprenaline and abolished the inhibitory action of carbachol on the isoprenaline response. 2. Phenylephrine in the presence of propranolol produced a positive inotropic effect and prolonged action potential duration through activation of alpha 1-adrenoceptors. Both of the effects of phenylephrine were significantly enhanced by PTX pretreatment. 3. Accumulation of [3H]inositol monophosphate (IP1) in papillary muscles prelabeled with myo-[3H]inositol was increased by phenylephrine in a concentration-dependent manner, which was antagonized by prazosin. Although PTX pretreatment significantly elevated the basal level of [3H]IP1 formation, the phenylephrine-induced increase in [3H]IP1 formation was unaffected. 4. It is concluded that the cardiac responses to alpha 1-adrenoceptor stimulation studied in these experiments are not transduced by a PTX sensitive G protein (Gi). However, the positive inotropic effect and prolongation of action potential duration mediated by alpha 1-adrenoceptor may be negatively regulated by Gi.
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PMID:Enhancement of the positive inotropic effect mediated by alpha 1-adrenoceptors in pertussis toxin-treated rabbit papillary muscles. 795 41

The purpose of these studies was to examine the effects of hypoxia on alpha 1-adrenergic receptor (alpha 1AR) mediated phosphatidylinositol (PI) turnover in cultured neonatal rat cardiac myocytes. Cells were pre-labeled with [3H]-inositol and incubated for 1 h in either normoxia or hypoxia. Phenylephrine, an alpha 1AR agonist, was added at various time intervals (0-60 min) before termination of the incubation. There was a time-dependent release of radioactivity from the lipid fraction to the aqueous fraction with alpha 1AR stimulation. alpha 1AR-mediated PI turnover was biphasic in normoxic cells and monophasic in hypoxic cells. Using ion-exchange chromatography, radioactivity in the inositol trisphosphate (IP3) peak was increased with acute phenylephrine stimulation (5 min) in the normoxic cells, while inositol phosphate (IP) and inositol bisphosphate (IP2) were increased with chronic stimulation (60 min). After 5 min of alpha 1AR stimulation, hypoxia did not alter total aqueous radioactivity when compared to normoxia, but there was a significant increase in IP2. However, there was decreased PI turnover in chronically stimulated (30-60 min) hypoxic cells when compared to normoxic cells. Hypoxia had no effect on radioactivity in the IP3 fraction with either 0, 5, or 60 min of alpha 1AR stimulation, but there was a significant increase in [1,4,5]-IP3 in hypoxic cells with 30 s alpha 1AR stimulation. With hypoxia, there was no difference in radioactivity in the phosphatidylinositols with either 0 or 5 min stimulation when compared to normoxia. However, after 60 min of alpha 1AR stimulation, hypoxia resulted in increased PI and PIP, when compared to normoxic cells, but PIP2 radioactivity was unchanged. There was no effect of pertussis toxin on either the acute or chronic phase of PI turnover, negating involvement of Gi or G(o). These data suggest that alpha 1AR stimulation in neonatal rat cardiac myocytes is biphasic, and that hypoxia produces a slower monophasic response during extended alpha 1-agonist exposure as would be found with ischemia.
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PMID:Alterations in alpha 1-adrenergic receptor-mediated phosphatidylinositol turnover in hypoxic cardiac myocytes. 826 53

In the present study, we investigated the mechanism of phenylephrine (alpha-1-adrenergic receptor agonist)-induced arachidonic acid release in Japanese white rabbit aortic smooth muscle cells (SMC). When introduced into permeabilized smooth muscle cells, guanosine S-[gamma-thio] triphosphate (GTPgamma S), which activates GTP-binding proteins (G proteins), stimulated arachidonic acid (AA) release. Neomycin, an inhibitor of phosphoinositide (PI) turnover, was almost without effect on GTP[gamma S] stimulated AA release. In addition, pertussis toxin (PT) partially inhibited phenylephrine-stimulated AA release, suggesting that IAP (Islet activating protein)-sensitive G proteins mediate this process. Phenylephrine-stimulated AA release was also inhibited by decreased extracellular calcium and aristolochic acid, suggesting a role for a phospholipase A2 (PLA2). Next PLA2 is reported to be a substrate for mitogen-activated protein (MAP) kinase. We examined the effect of phenylephrine on MAP kinase and c-jun N-terminal kinase (JNK) phosphorylation. Phenylephrine didn't induce phosphorylation of MAP kinase, but did induce phosphorylation of JNK. In addition, cells which were pretreated with PT inhibited the phosphorylation of JNK. These results suggest that IAP-sensitive G protein is involved in the coupling between alpha1-adrenergic receptor (AR) and PLA2 in cultured rabbit aortic SMCs, and that the alpha1-AR-induced AA release is mediated by JNK.
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PMID:alpha-1-Adrenergic receptor stimulation causes arachidonic acid release through pertussis toxin-sensitive GTP-binding protein and JNK activation in rabbit aortic smooth muscle cells. 860 77

Somatostatin (SS) and noradrenaline (NA) are distributed in the rat cerebral cortex, and seizure activity is one of the aspects of behavior affected by both neurotransmitters. Due to the possible interaction between both neurotransmitter systems, we studied whether phenylphrine, an alpha 1-adrenoceptor agonist, and prazosin, an alpha 1-adrenoceptor antagonist, can modulate SS-like immunoreactivity (SS-LI) levels, binding of [125I][Tyr11]SS to its specific receptors, the ability of SS to inhibit adenylate cyclase (AC) activity, and the guanine nucleotide binding regulatory protein G, and G., in the Sprague-Dawley rat frontoparietal cortex. An IP dose of 2 or 4 mg/kg of phenylephrine injected 7 h before decapitation decreased the number of SS receptors and increased the apparent affinity in frontoparietal cortex membranes. An IP dose of 20 or 25 mg/kg of prazosin administered 8 h before decapitation increased the number of SS receptors and decreased their apparent affinity. The administration of prazosin before the phenylephrine injection prevented the phenylephrine-induced changes in SS binding. The addition of phenylephrine and/or prazosin 10(-5) M to the incubation medium changed neither the number nor the affinity of the SS receptors in the frontoparietal cortex membranes. Phenylephrine or prazosin affected neither SS-LI content nor the basal or forskolin (FK)-stimulated AC activities in the frontoparietal cortex. In addition, SS caused an equal inhibition of AC activity in frontoparietal cortex membranes of phenylephrine-and prazosintreated rats compared with the respective control group. Finally, phenylephrine and prazosin did not vary the pertussis toxin (PTX)-catalyzed ADP ribosylation of Gi- and/or Go-proteins. These results suggest that the above-mentioned changes are related to the phenylephrine activation of alpha 1-adrenoceptors or to the blocking of these receptors by prazosin. In addition, these data provide further support for a functional interrelationship between the alpha 1-adrenergic and somatostatinergic systems in the rat frontoparietal cortex.
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PMID:Effect of phenylephrine and prazosin on the somatostatinergic system in the rat frontoparietal cortex. 874 58

1. The subtypes of alpha-adrenoceptor mediating the contractile responses of the cauda epididymis of the guinea-pig were investigated. The alpha 1-adrenoceptor agonist phenylephrine, but not the alpha 2-adrenoceptor agonist, xylazine (up to 10 microM), elicited concentration-dependent contractions from preparations of cauda epididymis (EC50 3.4 microM). The L-type Ca2+ channel antagonist, nifedipine (10 microM), reduced the maximal response to phenylephrine (by 77%). Preincubation of tissues with the alpha 1B-adrenoceptor-alkylating agent, chloroethylclonidine (50 microM, 30 min), shifted phenylephrine concentration-response curves to the right (4 fold) only when the alpha 2-adrenoceptor antagonist idazoxan (100 nM) was included during the pre-incubation with chloroethylclonidine. 2. Xylazine (1 microM) significantly shifted phenylephrine concentration-response curves to the left (3 fold); this effect was attenuated by idazoxan (100 nM). Both the incubation of preparations with nifedipine (10 microM) and the pre-incubation of preparations with chloroethylclonidine (50 microM, 30 min) attenuated the potentiating effects of xylazine (1 microM). Protection of alpha 2-adrenoceptors with idazoxan (100 nM) during the chloroethylclonidine (50 microM, 30 min) incubation restored the xylazine-mediated enhancement of phenylephrine concentration-response curves. Pertussis toxin (200 ng ml-1, 24 h) attenuated the xylazine (1 microM)-mediated potentiation of phenylephrine concentration-response curves. 3. Following the pre-incubation of preparations with chloroethylclonidine (50 microM, 30 min) 5-methylurapidil (10 nM to 3 microM) shifted phenylephrine concentration-response curves, in parallel, to the right with mean pKB values in the range of 8.27 (at 10 nM 5-methylurapidil) to 7.76 (at 3 microM 5-methylurapidil), the addition of idazoxan (100 nM) to the incubation medium did not significantly affect the 5-methylurapidil (10 to 300 nM) pKB values (8.41 to 7.64, respectively). In the presence of both idazoxan (100 nM) and nifedipine (10 microM), and following the pre-incubation with chloroethylclonidine (50 microM, 30 min), 5-methylurapidil (30 to 300 nM) still shifted phenylephrine concentration-response curves to the right (pKB values 7.77 to 7.36, respectively). 4. Phenylephrine (1 microM to 1 mM) increased the accumulation of [3H]-inositol phosphates (10 fold) in preparations of cauda epididymis (EC50 12 microM). This effect was sensitive to chloroethylclonidine pretreatment (50 microM, 30 min), antagonized with low affinity by 5-methylurapidil (- log pKi 7.8), but not potentiated by xylazine (1 microM). Xylazine (10 nM - 100 microM) reversed the forskolin (10 or 30 microM) stimulated accumulation of [3H]-adenosine 3':5'-cylic monophosphate (cyclic AMP) in preparations of cauda epididymis (by approximately 45%). Incubation of tissues with both pertussis toxin (200 ng ml-1, 24 h) and pertussis toxin vehicle increased the basal activity of adenylate cyclase (3 fold) but did not increase the capacity of forskolin (30 microM) to stimulate the accumulation of [3H]-cyclic AMP in these tissues. Xylazine did not significantly inhibit the forskolin-stimulated accumulation of [3H]-cyclic AMP in either vehicle or pertussis toxin treated tissues. 5. These studies indicate that the epididymis of the guinea-pig contains alpha 1- and alpha 2-adrenoceptors. On the basis of the actions of chloroethylclonidine and 5-methylurapidil the alpha 1-adrenoceptors of this tissue may be of the alpha 1A- and alpha 1B-subtypes and are linked to both the influx of extracellular Ca2+ and to phospholipase C. The alpha 2-adrenoceptors of this tissue are negatively coupled to adenylate cyclase, sensitive to pertussis toxin, but do not amplify phenylephrine-stimulated [3H]-inositol phosphate accumulation. Stimulation of the alpha 2-adrenoceptors of this tissue may selectively potentiate the influx of extracellular Ca2+.
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PMID:Alpha-adrenoceptor mediated responses of the cauda epididymis of the guinea-pig. 893 24

Both beta- and alpha(1)-adrenoceptors mediate the myocardial effects of catecholamines. It is well known that adenosine inhibits beta-dependent effects; however, whether alpha(1)-dependent responses can be similarly modulated is unclear. Accordingly, rat ventricular myocytes were exposed for 25 min to the alpha(1) agonist phenylephrine (2 microM, in the presence of 1 microM propranolol) in the absence or presence of adenosine (100 microM) or the A(1) receptor-selective agonist N(6)-cyclopentyladenosine (CPA, 1 microM). We also investigated the effects of K(ATP) blockade with glibenclamide (1 microM), the protein kinase C inhibitor bisindolylmaleimide (20 nM), and pertussis toxin (300 ng/ml), which uncouples G(i) protein/receptor interaction, and assessed whether effects of adenosine were mimicked by K(ATP) activation with either pinacidil or cromakalim (5 microM). Phenylephrine significantly increased cell shortening by 190% and the Ca(2+) transient by 24%, which was abolished by either adenosine or CPA, but not in the presence of the A(1) receptor-selective antagonist 8-cyclopentyl-1, 3-dipropylxanthine (1 microM), and was abolished by pertussis toxin. The effect of adenosine or CPA was reversed by glibenclamide and mimicked by either cromakalim or pinacidil. Bisindolylmaleimide was without effect. The A(2) or A(3) receptor agonists 2-(4-(2-carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamidoade nos ine and N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (1 microM each), respectively, were without effect. Neither CPA nor adenosine modulated the effect of endothelin-1 (5 nM), which also acts via the phosphoinositide hydrolysis pathway. We conclude that adenosine selectively inhibits alpha(1)-adrenergic-mediated effects in rat ventricular myocytes through a G(i) protein-dependent mechanism involving A(1) receptor and K(ATP) activation. Our study further suggests that endogenous adenosine may modulate alpha(1)-mediated effects of catecholamines.
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PMID:Inhibition of alpha(1)-adrenergic-mediated responses in rat ventricular myocytes by adenosine A(1) receptor activation: role of the K(ATP) channel. 1090 Feb 59

1. We investigated whether catecholamines through activation of alpha(1)-adrenergic receptors (alpha(1)-AR) are involved in mouse uterine contraction at parturition. Myometrial phospholipase C (PLC) activity and uterine contraction were measured in response to noradrenaline (NA), the specific alpha(1)-AR agonist phenylephrine (Phe) and oxytocin (OT). 2. Using the reverse transcription-polymerase chain reaction RT-PCR, we detected the alpha(1a)-AR subtype in late pregnant mouse myometrium. We also detected, by immunoblotting studies, PLCbeta(1), PLCbeta(3) and different alpha-subunits of pertussis toxin-insensitive (Galpha(q/11)) and -sensitive G proteins (Galpha(o/i3), Galpha(i1/2)). 3. Phenylephrine and NA did not alter the myometrial inositol phosphate (InsP) production of late pregnant or parturient mouse. In similar conditions, OT increased InsP production in a dose-dependent manner. Consistent with these results, only OT (10 microM) recruited PLCbeta(1) and PLCbeta(3) to myometrial plasma membranes. The OT-induced InsP response was not altered by pertussis toxin (300 ng ml(-1), 2 h pretreatment), suggesting the involvement of a member of the Galpha(q) family. 4. Noradrenaline and Phe failed to increase uterine contraction at late pregnancy and at parturition. In contrast, OT induced uterine contraction in a dose-dependent manner with maximal increase (400 %) at a concentration of 1 microM. 5. The results indicate that OT receptors (OTR) but not alpha(1)-AR are linked to myometrial PLC activation and uterine contraction in late pregnant and parturient mouse. This discrepancy between mouse and other mammals could be attributed to the alpha(1)-AR subtype expressed in myometrium at this time.
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PMID:Catecholamines are not linked to myometrial phospholipase C and uterine contraction in late pregnant and parturient mouse. 1157 62

The actions of noradrenaline (NA) on the neurons acutely isolated from paratracheal ganglia of rats and the ionic mechanisms involved were studied with nystatin-perforated patch recording configuration. Under current-clamp conditions, application of 10 microM NA produced membrane depolarization followed by repetitive action potentials. NA evoked an inward cationic current under voltage-clamp conditions at a holding potential of -60 mV. Transient tail inward ('hump') current was also induced by washout of NA. The NA-induced current was reduced by extracellular Ca(2+) and Mg(2+), with half-maximal concentrations of 0.7 and 2.6 mM for Ca(2+) and Mg(2+), respectively. Phenylephrine, an alpha(1)-adrenoceptor agonist, mimicked the NA-induced current, but the 'hump' current did not occur upon washout of phenylephrine. The NA-induced current was inhibited by prazosin and WB-4101, alpha(1)-adrenoceptor antagonists. In contrast, in the presence of yohimbine, an alpha(2)-adrenoceptor antagonist, the NA-induced current was potentiated and the washout of NA failed to evoke the 'hump' current. The pretreatment of paratracheal neurons with pertussis toxin also potentiated the NA-induced current. The NA-induced inward current was inhibited by pretreatment with U73122, a phospholipase C inhibitor, and xestospongin-C, a membrane-permeable IP(3) receptor antagonist. On the other hand, thapsigargin, BAPTA-AM and calmidazolium had no effect on the NA-induced current, suggesting that release of Ca(2+) from intracellular Ca(2+) stores via IP(3) receptors is not involved in the NA action. The cationic channels activated by NA play an important physiological role in neuronal membrane depolarization in rat paratracheal ganglia.
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PMID:Noradrenaline-induced cation currents in isolated rat paratracheal ganglion neurons. 1536 21


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