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)

Neuropeptide Y (NPY) receptors in the SK-N-MC human neuroblastoma cell line couple to mobilization of intracellular Ca2+ and inhibition of adenylylcyclase. Pretreatment of SK-N-MC cells with isoproterenol enhanced the NPY-stimulated Ca2+ mobilization, mainly by increasing the maximal response to NPY. The enhancement was time-(maximal after 24 h) and concentration-dependent (maximal at 10 microM isoproterenol), blocked by the beta-adrenergic antagonist propranolol, and mimicked by forskolin. Concomitant treatment with cycloheximide prevented the enhancing effect of isoproterenol, suggesting the involvement of protein synthesis. Isoproterenol treatment did not alter the number or affinity of 125I-labeled NPY binding sites, the amount of pertussis toxin substrates, or NPY-mediated inhibition of cAMP accumulation. Similarly, isoproterenol treatment had no effect on basal intracellular Ca2+ and on Ca2+ increases elicited by carbachol, caffeine, or ionomycin. We conclude that isoproterenol treatment can sensitize NPY receptor responsiveness in a way that is specific for Ca2+ mobilization mechanisms used by this hormone.
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PMID:NPY-stimulated Ca2+ mobilization in SK-N-MC cells is enhanced after isoproterenol treatment. 131 94

The LAN-1 clone, a cell line derived from a human neuroblastoma, possesses muscarinic receptors. The stimulation of these receptors with increasing concentrations of carbachol (CCh; 1-1,000 microM) caused a dose-dependent increase of the intracellular free Ca2+ concentration ([Ca2+]i). This increase was characterized by an early peak phase (10 s) and a late plateau phase. The removal of extracellular Ca2+ reduced the magnitude of the peak phase to approximately 70% but completely abolished the plateau phase. The muscarinic-activated Ca2+ channel was gadolinium (Gd3+) blockade and nimodipine and omega-conotoxin insensitive. In addition, membrane depolarization did not cause any increase in [Ca2+]i. The CCh-induced [Ca2+]i elevation was concentration-dependently inhibited by pirenzepine and 4-diphenylacetoxy-N-methylpiperidine methiodide, two rather selective antagonists of M1 and M3 muscarinic receptor subtypes, respectively, whereas methoctramine, an M2 antagonist, was ineffective. The coupling of M1 and M3 receptor activation with [Ca2+]i elevation does not seem to be mediated by a pertussis toxin-sensitive guanine nucleotide-binding protein or by the diacylglycerol-protein kinase C system. The mobilization of [Ca2+]i elicited by M1 and M3 muscarinic receptor stimulation seems to be dependent on an inositol trisphosphate-sensitive intracellular store. In addition, ryanodine did not prevent CCh-induced [Ca2+]i mobilization, and, finally, LAN-1 cells appear to lack caffeine-sensitive Ca2+ stores, because the methylxanthine was unable to elicit intracellular Ca2+ mobilization, under basal conditions, after a subthreshold concentration of CCh (0.3 microM), or after thapsigargin.
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PMID:LAN-1: a human neuroblastoma cell line with M1 and M3 muscarinic receptor subtypes coupled to intracellular Ca2+ elevation and lacking Ca2+ channels activated by membrane depolarization. 131 63

Metabotropic glutamate receptor (mGluR) is highly expressed in cerebellar Purkinje cells. The purpose of this study was pharmacological and immunocytochemical characterization of the mGluR in single cerebellar neurons, especially Purkinje cells. Ca2+ imaging with fura-2 in cultured cerebellar neurons, identified immunocytochemically, was used to record the direct effects of drugs in stable conditions. In addition, the expression of mGluR was examined, and expression of the intracellular receptor for inositol trisphosphate (IP3) produced by mGluR activation was studied immunocytochemically with specific antibodies. Purkinje neurons and some other neurons showed Ca(2+)-mobilizing responses to mGluR agonists. These responses were mediated by mGluR because they were not blocked by ionotropic GluR antagonists, were independent of the caffeine-sensitive Ca2+ pool, and were blocked by inhibitors of IP3-induced Ca2+ release. This is the first pharmacological characterization of mGluR at single Purkinje cells. The results differed as follows from those in earlier studies in which phosphoinositide turnover of the entire population of cerebellar cells was monitored: (1) the mGluR responses were not blocked by pertussis toxin or D,L-2-amino-3-phosphonopropionic acid; (2) glutamate was a potent agonist, whereas L-aspartate was ineffective; and (3) the dose-response relationship showed an all-or-none tendency. The metaboltropic response of Purkinje cells changed markedly during development, with a sharp peak after day 4 of culture, whereas mGluR and IP3 receptor proteins increased steadily during maturation. This apparent desensitization of mGluR was not blocked by inhibitors of protein kinase C (PKC) or ADP-ribosyltransferase. The metabotropic responses were mainly localized to the center of the somata of Purkinje cells even on day 4, whereas both receptor proteins were expressed throughout the cell. These results suggest that the function of mGluR is spatially and developmentally controlled by a posttranslational mechanism involving a mechanism other than phosphorylation by PKC or ADP-ribosylation.
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PMID:Pharmacological and immunocytochemical characterization of metabotropic glutamate receptors in cultured Purkinje cells. 133 61

1. Direct actions of strychnine (Str) and brucine (Bru) on the dissociated hippocampal CA1 neurones of the rat have been investigated with the whole-cell mode of the patch-clamp technique. 2. At a holding potential (VH) of -20 mV, both Str and Bru elicited outward current at concentrations over 10(-5) M. The reversal potential of Str-induced current (EStr) was -77.8 mV, which was close to the K+ equilibrium potential (EK = -80.3 mV). The change in EStr for a ten fold change in extracellular K+ concentration was 58 mV, indicating that the membrane behaves like a K+ electrode in the presence of Str. 3. The concentration-response curves for Str and Bru were bell-shaped, and nearly maximum response occurred at 10(-4) M for Str and 3 x 10(-4) M for Bru. The maximum current amplitude induced by Bru was about 80% of that induced by Str. A transient 'hump' current appeared immediately after the wash-out of external solutions containing Str and Bru at concentrations higher than 10(-4) and 3 x 10(-4) M, respectively. 4. The Str-induced current (IStr) was antagonized by K+ channel blockers such as Ba2+, tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. IStr was insensitive to glibenclamide, a blocker of ATP-sensitive K+ channels. 5. Internal perfusion with 10 mM BAPTA did not affect the Str-induced IK. Depletion of the intracellular Ca2+ store by caffeine had no effect, indicating that intracellular Ca2+ does not mediate the Str-induced activation of K+ conductance.6. Both guanosine-5'-0-3-thiotriphosphate (GTPyS) and guanosine-5'-O-thiodiphosphate (GDPPS) suppressed the Str-induced IK, the former action appearing more rapidly than the latter. The results suggest that the GTP binding proteins are involved in this Str response.7. When neurones were loaded with cholera toxin (CTX) or pertussis toxin (PTX) through a patch pipette, PTX suppressed the Str response whereas CTX did not, suggesting that G, and/or Go might be involved in the Str-induced IK.
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PMID:Strychnine-induced potassium current in CA1 pyramidal neurones of the rat hippocampus. 135 68

1. Single smooth muscle cells obtained by enzymic dispersion of the longitudinal muscle layer of guinea-pig ileum were used for recording membrane currents under whole-cell voltage clamp in response to carbachol (100 microM, unless otherwise stated) or histamine (100 microM) applied extracellularly. 2. At a holding potential of 0 mV, a transient outward current was evoked by carbachol and histamine. Responses to the two agonists were very similar in size and time course to the current response to caffeine (10 mM). The response to carbachol was virtually absent in the presence of histamine, and vice versa. Caffeine was without effect in the presence of either of these agonists. Inclusion of EGTA (10 or 20 mM) in the pipette abolished the responses to carbachol, histamine and caffeine. Thus, the outward current responses were considered to represent opening of Ca(2+)-activated K+ channels in response to a massive release of Ca2+ from the same stores by these three agents. 3. An inward current was evoked by carbachol and histamine, but not by caffeine at a holding potential of -40 mV, which was considered to represent opening of cationic channels. The carbachol-induced inward current was much longer in duration and larger in size than the histamine-induced inward current. 4. Inclusion of GDP beta S (2 mM) in the pipette abolished the inward and outward current responses to histamine, but inhibited only part of those to carbachol. 5. When the holding potential was held at 0 mV with inclusion of GTP gamma S (0.1-1 mM) in the pipette, spontaneous transient outward currents appeared immediately after break-through but disappeared a few minutes later. Under these conditions, caffeine (10 mM) was almost without effect, suggesting that GTP gamma S had released Ca2+ stores. When the holding potential was held at -40 mV and GTP gamma S (0.1 or 0.2 mM) was present in the pipette, an inward current developed a few minutes after break-through. During the GTP gamma S-induced inward current, application of carbachol or histamine produced no further inward current. However, when 0.01 mM-GTP gamma S was included in the pipette solution, carbachol- and histamine-induced inward currents were potentiated. 6. Pretreated with 2-5 micrograms/ml pertussis toxin (PTX) did not change noticeably the outward current responses to carbachol and histamine, but abolished or markedly reduced the inward current responses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GTP-binding protein involvement in membrane currents evoked by carbachol and histamine in guinea-pig ileal muscle. 143 5

1. Membrane currents were recorded by a patch-clamp pipette technique in cultured cells from rat portal vein using the whole-cell mode. 2. Noradrenaline (NA, 10(-5) M) and phorbol-12,13-dibutyrate (PDBu, 10(-7) M) produced an increase in voltage-dependent inward current carried by barium (5 mM), but their effects were not additive. Calcium-activated chloride current was evoked by NA but not by PDBu. 3. The NA-induced increase in peak voltage-dependent inward current was inhibited by intracellular application of GDP-beta-S (10(-3) M) while the effect of PDBu was unchanged. GDP-beta-S blocked the NA-induced chloride current but had no effect on the caffeine-induced chloride current. 4. Inclusion of GTP-gamma-S (10(-5)-10(-4) M) in the pipette solution increased the voltage-dependent inward current and inhibited the NA- or PDBu-induced increase in peak current. GTP-gamma-S potentiated the effect of NA on calcium-activated chloride current. At higher concentrations (10(-3) M), GTP-gamma-S activated the chloride current and prevented the effects of NA or caffeine on this current. 5. The combination of 10(-5) M-aluminium chloride and 10(-2) M-sodium fluoride had an effect similar to that of high concentrations of GTP-gamma-S on both inward current and calcium-activated chloride current. In contrast, arachidonic acid (10(-3) M) had no effect on calcium and chloride conductances activated by NA. 6. Cells responded normally to NA after pre-treatment for 4-30 h with 10 micrograms ml-1 pertussis toxin (PTx). 7. It is concluded that the stimulation of calcium and chloride conductances by NA is mediated through activation of a PTx-insensitive GTP-binding protein. This effect may involve activation of phospholipase C enzyme and production of both D-myo-inositol 1,4,5-trisphosphate which depletes calcium stores and diacylglycerol which activates protein kinase C.
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PMID:GTP-binding proteins mediate noradrenaline effects on calcium and chloride currents in rat portal vein myocytes. 170 Jan 11

Effects of norepinephrine (NE) on voltage-dependent Ca channel current (ICa) were examined applying whole cell patch-clamp technique to single smooth muscle cells freshly isolated from vas deferens of the guinea pig. K currents and contraction of the cell were abolished by Cs and EGTA in the pipette solution, respectively. The peak ICa and Ba current (IBa) elicited by depolarization from -60 mV in a solution containing 2.2 mM Ca or Ba were reduced by 10-60% in voltage- and dose-dependent manners by the application of NE or phenylephrine. This effect was greatly attenuated in the presence of prazosin. The decrease in IBa was always smaller than that in ICa at any potential. Even after simultaneous application of 5 mM caffeine and 10 microM NE to the cells in a Ba-containing solution, the second challenge with NE again reduced IBa in a similar manner. The decrease in IBa by 10 microM NE could not be explained well by a small shift (-5 mV) of the voltage dependence of the steady-state inactivation. The effect of NE on IBa was irreversibly enhanced by 0.1 mM guanosine 5'-O-(3-thiotriphosphate) and almost abolished by 1 mM guanosine 5'-O-(2-thiodiphosphate) added to the pipette solution but appeared not to be affected by the treatment with pertussis toxin. It can be concluded that, under these experimental conditions, the activation of alpha 1-adrenoceptor in vas deferens smooth muscle cells reduces Ca channel activity possibly via a mechanism involving GTP-binding protein in addition to Ca-mediated Ca channel inactivation mechanism.
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PMID:Mechanisms of NE-induced reduction of Ca current in single smooth muscle cells from guinea pig vas deferens. 184 70

The effects of the aqueous extract of leaves of Bridelia atroviridis (Bridelia), a small African tree, on the mechanical activity of rat uterus were studied. The aqueous extract of leaves of B atroviridis administered in a concentration-dependent manner (5 x 10(-6)-1.2 x 10(-3) g/ml) induced contractions that were antagonized by various calcium entry blockers (nifedipine, diltiazem, manganese chloride). In absence of external calcium ions, repeated applications of a supramaximal concentration of Bridelia (1.2 x 10(-3) g/ml) evoked sustained and repeated contractions the amplitude of which was congruent to 20% of those obtained in the physiological external calcium concentration. Bridelia-induced contractions in calcium-free medium were inhibited by isoprenaline (8 x 10(-7) M), caffeine (15 x 10(-3) M) and trifluoperazine (10(-5) M). Contractile responses induced by Bridelia in both calcium-containing and calcium-free media were antagonized by prior incubation of uterus with phorbol 12, 13-dibutyrate (6 x 10(-7) M), cholera toxin (6 x 10(-8) M) or pertussis toxin (5 x 10(-7) g/ml). These results show that Bridelia has a potent uterotonic action in the rat. The cellular basis of this action appears to be complex, and involves various mechanisms including calcium mobilization from both intra and extracellular compartments and activation of phospholipase C through a G-protein.
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PMID:The uterotonic action of the aqueous extract of Bridelia atroviridis in the rat. 191 13

An augmentation of psychostimulant-induced motor activity, termed sensitization, occurs with daily treatment and can last for months or years. At least in part, sensitization results from a long-term change in mesocorticolimbic dopamine transmission and may involve a disinhibition of dopamine neurons. Dopamine D2 autoreceptors and gamma-aminobutyric acidB (GABAB) receptors provide tonic inhibition to dopamine neurons via a G protein-mediated increase in K+ efflux. To evaluate the role of these inhibitory mechanisms in sensitization, pertussis toxin (PTX) was injected into the A10 dopamine region to uncouple the receptors via ADP-ribosylation of G proteins. In this study we demonstrated a significant augmentation in cocaine-stimulated motor activity, at doses greater than 3.0 mg/kg, 14 days after intra-A10 injection of PTX. Also, amphetamine-, but not morphine- or caffeine-stimulated motor activity was significantly augmented 2 weeks after PTX pretreatment. In vivo microdialysis revealed an augmentation of cocaine-induced increases in extracellular dopamine in the nucleus accumbens 14 days after PTX pretreatment. Pretreatment in the A10 region with the GABAB agonist baclofen, blocked cocaine-stimulated motor activity in control animals, but not in PTX-pretreated animals, indicating that the PTX treatment had uncoupled the GABAB receptor. Footshock stress activates mesocortical dopamine transmission, and postmortem tissue levels of dihydroxyphenylacetic acid and homovanillic acid in the prefrontal cortex were increased in PTX-pretreated animals. We hypothesize that the sensitized responses to cocaine, amphetamine and stress produced by PTX results from a decrease in dopamine D2 and GABAB-mediated inhibitory control of A10 dopamine neurons.
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PMID:Sensitization to psychostimulants and stress after injection of pertussis toxin into the A10 dopamine region. 194 36

We studied the effect of adenosine on Na+/Ca2+ exchange activity in ewe heart ventricular sarcolemmal vesicles. Adenosine was found to stimulate Na+/Ca2+ exchange activity in a dose-dependent manner from 0.1 nM to 10 microM, with maximal stimulation (40%) at 0.1 microM adenosine. The Vmax of Na+/Ca2+ exchange was increased, but the Km for Ca2+ was not altered. The effect of adenosine was specific since 1 microM adenine, inosine, and guanosine led to less than 15% stimulation, and adenosine diphosphate had no effect. Caffeine antagonized the activation of Na+/Ca2+ exchange by adenosine, and the order of potency of adenosine analogs was N6-(L-2-phenylisopropyl)adenosine = N6-cyclohexyladenosine = 5'-(N- ethylcarboxamido)adenosine much greater than N6-(D-2-phenylisopropyl)adenosine, indicating the involvement of A1 subclass receptors. The effect of adenosine was mimicked by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and blocked by pertussis toxin treatment. Taken together, these results suggest that A1 subclass receptors coupled to a pertussis toxin-sensitive G protein mediate the activation of Na+/Ca2+ exchange activity by adenosine. We conclude that the negative inotropic effect of adenosine in ventricular muscle, antagonistic toward cyclic AMP, may involve activation of Na+/Ca2+ exchange.
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PMID:Activation of Na+/Ca2+ exchange by adenosine in ewe heart sarcolemma is mediated by a pertussis toxin-sensitive G protein. 212 Feb 8


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