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)

1. In order to determine the intracellular mechanisms by which galanin induces contraction of isolated smooth muscle cells from pig ileum, we examined the effects of external Ca2+, relaxing agents, pertussis toxin and forskolin on the galanin-induced contraction and compared these effects to those observed on the cholecystokinin derivative CCK8-induced contraction. 2. Galanin induced a concentration-dependent cell contraction. The maximal contraction (24.5 +/- 2.1% of the length of resting cells) was observed at 1 nM of galanin. When cells were incubated in the simultaneous presence of concentrations of galanin (10 fM) and CCK8 (1 pM) which were ineffective alone, or galanin (10 fM) and acetylcholine (100 pM), a synergistic action was observed corresponding to a submaximal contraction. 3. Incubation of cells in Ca(2+)-free medium caused a significant decrease in galanin- but not in CCK-induced contraction. Nifedipine, a Ca2+ channel blocker, provoked a concentration-dependent inhibition of galanin-induced contraction while it had no effect on the contraction induced by CCK8. 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin. 5. When cells were pre-incubated for 3 h in the presence of 200 ng/ml of pertussis toxin, the contraction induced by galanin was abolished while the CCK-induced contraction remained unchanged. On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction. 6. These results indicate that galanin induces a concentration-dependent contraction of pig ileum smooth muscle by a direct myogenic effect. This effect of galanin involves the activation of a pertussis toxin-sensitive G protein, which results in an influx of Ca2+ into the cell. This intracellular pathway is insensitive to the relaxing effect of cAMP.
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PMID:Intracellular pathways triggered by galanin to induce contraction of pig ileum smooth muscle cells. 128 68

1. Endothelin-1 (ET-1)-induced contraction of porcine coronary artery strips may be mediated via at least two intracellular signalling mechanisms, the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels and the stimulation of phosphoinositide breakdown. Here we have investigated the possible involvement of pertussis toxin (PT)-sensitive guanosine-5'-triphosphate (GTP)-binding proteins (G-proteins) in ET-1-induced activation of these two signalling pathways in porcine coronary artery smooth muscle. 2. Increase in extracellular K+ concentration (10, 15 mM) shifted the dose-response relationship for the ET-1-induced contraction to the left. 3. The dihydropyridine Ca2+ channel blocker, nifedipine (10(-8) M), induced a rightward shift in the dose-response curve for ET-1. Pretreatment of the arterial strips with PT (0.1 microgram ml-1) induced a similar rightward shift of the ET-1 dose-response curve but not of the KCl response. Nifedipine (10(-8) M) did not further attenuate the ET-1-induced contraction in the PT-pretreated strips. 4. The pretreatment with PT significantly reduced 45Ca2+ uptake of the arterial strips stimulated by ET-1, but had no effect on ET-1-induced production of inositol phosphates. 5. The contractile response of the arterial strips to phorbol dibutyrate, an active phorbol ester, was not significantly affected by 10(-8) M nifedipine. 6. We confirmed that the pretreatment of the tissue with PT induced ADP-ribosylation of a 41 kDa membrane protein. 7. These findings indicate that activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels by ET-1 in this tissue is mediated via a PT-sensitive G-protein in a manner apparently independent of the ET-1-induced activation of protein kinase C. It is concluded that the action of ET-1 in porcine coronary artery is mediated via two distinct signal transduction pathways, which are coupled to PT-sensitive and PT-insensitive GTP-binding proteins, respectively.
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PMID:A pertussis toxin-sensitive mechanism of endothelin action in porcine coronary artery smooth muscle. 133 Jan 78

The effects of gamma-aminobutyric acid (GABA) and isoguvacine on the thyrotropin (TSH) secretion stimulated by thyrotropin releasing hormone (TRH), were investigated in vitro with perifused rat pituitaries. At nanomolar concentrations the two agonists induced potentiation of the TRH-induced TSH release. The potentiation was blocked by SR 95531 a specific GABAA antagonist. The isoguvacine potentiation of the TSH response to TRH failed to occur when cobalt (Co2+) was added to the perifused medium. Nifedipine completely blocked the GABA or isoguvacine potentiation of the TSH response while omega-conotoxin did not modify it. Pre-perifusion of the pituitaries with pertussis toxin did not change the TSH response to TRH but completely inhibited the isoguvacine potentiation of the response. Our results demonstrate that the GABA potentiation of TRH-induced TSH release occurring through the stimulation of GABAA receptor sites is a calcium (Ca2+)-dependent phenomenon, probably mediated by activation of dihydropyridine (DHP)-sensitive, omega-conotoxin-insensitive Ca2+ channels involving a pertussis toxin-sensitive G protein.
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PMID:Involvement of dihydropyridine-sensitive calcium channels in the GABAA potentiation of TRH-induced TSH release. 170 71

1. Voltage-activated Ca2+ channel currents were recorded from cultured rat dorsal root ganglion (DRG) neurones using the whole-cell clamp technique with Ba2+ as the charge carrier. 2. Inclusion of the GTP analogue guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S, 500 microM) or guanylylimidodiphosphate (GMP-PNP, 500 microM) or GTP itself (1 mM) in the patch pipette solution resulted in a smaller, slowly activating Ca2+ channel current which did not inactivate during a 100 ms voltage step. This current was inhibited by CdCl2 (10-100 microM) and omega-conotoxin (1 microM). 3. Nifedipine (5 microM), (-)-(R)-201-791 (5 microM), D600 (10 microM), and diltiazem (30 microM) inhibited Ca2+ channel currents recorded from control neurones, although in some cells a biphasic response was observed, with an initial increase preceding the inhibition of the currents. In the presence of internal GTP-gamma-S, at a holding potential (VH) of -80 mV, only potentiation of the Ca2+ channel current was observed in the presence of all three Ca2+ channel ligands. Internal GMP-PNP, while less effective than GTP-gamma-S, also resulted in D600 showing an agonist response. Similarly, in the presence of internal GTP (1 mM), (-)-(R)-202-791 gave a prolonged agonist response. 4. Nifedipine, whether acting as an antagonist in control cells or as an agonist in GTP-gamma-S-containing cells, induced a shift to more hyperpolarized potentials of the steady-state inactivation curves. 5. Potentiation of Ca2+ channel currents induced by D600 in GTP-gamma-S-containing cells, was not observed when the neurones were pre-treated with pertussis toxin. The presence of internal GDP-beta-S (500 microM) did not significantly alter the maximum inhibitory action of D600 compared with controls. However, 1 mM-GDP-beta-S increased the rate of onset of inhibition by (-)-(R)-202-791. 6. Depolarizing VH to -30 mV accelerated the onset of inhibition induced by the Ca2+ channel ligands in control cells. In the presence of internal GTP-gamma-S at VH -30 mV, biphasic responses were produced by all the Ca2+ channel antagonist ligands with initial stimulation for 1-2 min being followed by inhibition of the Ca2+ channel currents. 7. The agonist actions of (+)-(S)-202-791 were potentiated by the presence of internal GTP-gamma-S. 8. The expression of an agonist response to (-)-(R)-202-791 induced by internal GTP-gamma-S was also present in sympathetic neurones cultured from adult rat superior cervical ganglion (SCG).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interaction between calcium channel ligands and guanine nucleotides in cultured rat sensory and sympathetic neurones. 255 37

Platelet-derived growth factor (PDGF) and angiotensin II (AII) are thought to mediate their biological effects in vascular smooth muscle cells (VSMCs) by causing alterations in cytosolic free calcium ([ Ca2+]i). In this study we examine the pathways by which PDGF and AII alter [Ca2+]i in VSMCs. Addition of PDGF resulted in a rapid, transient, concentration-dependent increase in [Ca2+]i; this rise in [Ca2+]i was blocked completely by preincubation of cells with ethylene glycol-bis (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) or CoCl2, by the voltage-sensitive Ca2+-channel antagonists verapamil or nifedipine, by 12-O-tetradecanoylphorbol-13-acetate (TPA), or by pertussis toxin. AII also caused an increase in [Ca2+]i; however, AII-stimulated alterations in [Ca2+]i displayed different kinetics compared with those caused by PDGF. Pretreatment of cells with 8-(diethylamine)-octyl-3,4,5-trimethyoxybenzoate hydrochloride (TMB-8), almost totally inhibited AII-induced increases in [Ca2+]i. EGTA or CoCl2 only slightly diminished AII-stimulated increases in [Ca2+]i. Nifedipine, verapamil, TPA, and pertussis toxin pretreatment were without effect on AII-induced increases in [Ca2+]i. PDGF and AII both stimulated increases in total inositol phosphate accumulation, although the one-half maximal concentration (ED50) for alterations in [Ca2+]i and phosphoinisitide hydrolysis differed by a factor of 10 for PDGF (3 X 10(-10) M for Ca2+ vs. 2.5 X 10(-9) M for phosphoinositide hydrolysis), but they were essentially identical for AII (7.5 X 10(-9) M for Ca2+ vs. 5.0 X 10(-9) M for phosphoinositide hydrolysis). PDGF stimulated mitogenesis (as measured by [3H]-thymidine incorporation into DNA) in VSMCs with an ED50 similar to that for PDGF-induced alterations in phosphoinositide hydrolysis. PDGF-stimulated mitogenesis was blocked by pretreatment of cells with voltage-sensitive Ca2+ channel blockers, TPA, or pertussis toxin. These results suggest that PDGF and AII cause alterations in [Ca2+]i in VSMCs by at least quantitatively distinct mechanisms. PDGF binding activates a pertussis-toxin-sensitive Ca2+ influx into cells via voltage-sensitive Ca2+ channels (blocked by EGTA, verapamil, and nifedipine), as well as stimulating phosphoinositide hydrolysis leading to release of Ca2+ from intracellular stores. AII-induced alterations in [Ca2+]i are mainly the result of phosphoinositide hydrolysis and consequent entry of Ca2+ into the cytoplasm from intracellular stores. Our data also suggest that changes in [Ca2+]i caused by PDGF are required for PDGF-stimulated mitogenesis.
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PMID:Platelet-derived growth factor and angiotensin II cause increases in cytosolic free calcium by different mechanisms in vascular smooth muscle cells. 270 48

We previously reported that angiotensin-II (AII) stimulated and dopamine (DA) inhibited the release of human placental lactogen (hPL) from trophoblastic cells. The mechanisms of action involved in these endocrine regulations are poorly known. In this study, we investigated the role of Ca2+ as a potential cellular mediator of the effects of AII and DA. Incubation of freshly isolated human term trophoblastic cells with DA led to a dose-dependent inhibition of 45Ca2+ influx, with a maximum of 55 +/- 5% and an EC50 of 10 +/- 3 mumol/L. This DA-inhibited Ca2+ influx was reversed by spiperone, a D2-dopamine receptor antagonist. Preincubation of cells with pertussis toxin completely blocked the inhibitory effect of DA on placental 45Ca2+ influx. Nifedipine (10(-5) mol/L), like DA, inhibited 45Ca2+ influx (41 +/- 3% inhibition). Moreover, nifedipine decreased hPL release (57 +/- 10%; EC50, 0.25 +/- 0.09 mumol/L). Coincubation of DA and nifedipine did not enhance the inhibitory effects of these agents on either 45Ca2+ influx or hPL release. The incubation of trophoblastic cells with [Sar1]AII, a potent agonist of AII, led to a dose-dependent stimulation of 45Ca2+ influx. The maximal stimulation was 221 +/- 37% of the control value, with an EC50 of 50 +/- 15 nmol/L. This stimulation was inhibited by coincubation with the AII antagonist [Sar1,Ala8]AII. [Sar1]AII-stimulated Ca2+ influx was blocked by preincubation with pertussis toxin. Bay K 8644 also stimulated 45Ca2+ influx (238 +/- 41% of the control). Moreover, Bay K 8644 stimulated hPL release. The maximal stimulation was 180 +/- 22% of the control value, with an EC50 of 0.40 +/- 0.30 mumol/L. Coincubation of Bay K 8644 and AII did not led to additional stimulation of either 45Ca2+ influx or hPL release. These results suggest that Ca2+ influx is one mechanism that mediates AII and DA regulation of hPL release in human term trophoblastic cells.
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PMID:A role for extracellular calcium in the regulation of placental lactogen release by angiotensin-II and dopamine in human term trophoblastic cells. 769 Mar 61

Ca2+ fluxes were examined in HEK 293 cells stably expressing the rat or porcine calcitonin receptors (CTRs). Calcitonin (CT) rapidly increased cytosolic Ca2+ ([Ca2+]i) concentrations in these cells in a manner which was sustained in the presence of extracellular Ca2+ ([Ca2+]e). In cells pretreated with CT, elevation of the [Ca2+]e concentration resulted in a further increase in [Ca2+]i which was concentration-dependent with respect to both the concentration of CT and the increment of [Ca2+]e. Untransfected cells, cells transfected with vector alone, and CTR-transfected cells not treated with CT, were unresponsive to [Ca2+]e. The microsomal Ca(2+)-ATPase inhibitor thapsigargin was able to mimic both the acute [Ca2+]i fluxes and responsiveness to [Ca2+]e mediated by CT in these cells. The CT-induced responsiveness to [Ca2+]e was neither mimicked by, nor affected by, activators of the cAMP or protein kinase C pathways. Treatment of cells with pertussis toxin influenced neither the primary Ca2+ fluxes in response to CT or thapsigargin nor the agonist-induced [Ca2+]e influx. Nifedipine failed to block responses to either CT or thapsigargin. These results lead to the important conclusion that the CTR participates in receptor-activated Ca2+ inflow, in which depletion of intracellular Ca2+ pools leads secondarily to influx of extracellular Ca2+.
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PMID:Calcium inflow in cells transfected with cloned rat and porcine calcitonin receptors. 769 52

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)
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PMID:Effects of pertussis and cholera toxins on alpha-adrenoceptor function in rat tail artery: differences in hypertension. 790 52

In PC-12 cells differentiated with nerve growth factor, neuropeptide Y (NPY) potentiated the K(+)-evoked increase in intracellular calcium, but this potentiation was not mediated by classical Y1 or Y2 NPY receptors. The potentiation by NPY appeared to occur through the mobilization of calcium from intracellular stores because thapsigargin successfully blocked the potentiation. In contrast, the Y2 agonist, NPY-(13-36), attenuated the K(+)-evoked increase in intracellular calcium by decreasing the influx of extracellular calcium. The effect of NPY-(13-36) on dopamine release from PC-12 cells was next studied. NPY-(13-36) significantly attenuated the K(+)-evoked dopamine release in a concentration-dependent manner. Nifedipine and omega-conotoxin also attenuated the evoked dopamine release. In the presence of nifedipine or omega-conotoxin, NPY-(13-36) produced further inhibition of the evoked dopamine release. Furthermore, NPY-(13-36)-induced inhibition of dopamine release was abolished by pertussis toxin pretreatment. We conclude that the regulatory effects of NPY and analogues on intracellular calcium are mediated by multiple NPY receptor subtypes. Y2 receptor-mediated pertussis toxin-sensitive inhibition of the evoked dopamine release does not seem to be due to interactions with L- or N-type Ca2+ channels.
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PMID:Modulation of intracellular calcium transients and dopamine release by neuropeptide Y in PC-12 cells. 816 42

The signalling pathways used by the human endothelin A receptor to activate phospholipase A2 in Chinese hamster ovary cells were investigated. Pertussis toxin caused a partial but significant reduction in endothelin-1-induced arachidonic acid release although cAMP-dependent kinase inhibitors did not mimic its action. Extracellular calcium and its entry into the cell was essential for activation of phospholipase A2 as its removal from media or incubation with an intracellular calcium chelator-reduced activation. Nifedipine had no effect on endothelin-1-induced arachidonic acid release while divalent cations caused a significant reduction indicating the possible role of CRAC. Thapsigargin caused an increase in arachidonic acid release which was completely inhibited by pertussis toxin treatment. This further supports the involvement of CRAC in calcium influx and activation of phospholipase A2 by the human endothelin A receptor.
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PMID:Activation of phospholipase A2 by the human endothelin receptor in Chinese hamster ovary cells involves Gi protein-mediated calcium influx. 852 39


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