UMLS:C0043167 - FACTA Search

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

1. The effects of somatostatin (SS) on the low-voltage-activated and high-voltage-activated (HVA) Ca2+ channels in pyramidal neurons acutely dissociated from the hippocampal CA1 region of 2- to 3-wk-old rats were investigated in a nystatin perforated-patch recording configuration under voltage-clamp conditions. 2. SS had no effect on the low-voltage-activated Ca2+ channel but did inhibit the HVA Ca2+ channel in a concentration-, time-, and voltage-dependent manner. 3. SS showed the activation phase of Ba2+ current (IBa) passing through HVA Ca2+ channels, and the maximum inhibition was 28% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. Pretreatment with pertussis toxin (PTX) completely blocked the effect of SS on HVA IBa, suggesting the contribution of PTX-sensitive Gi/Go proteins to the SS-induced inhibition. 4. The applications of forskolin, 8-Br-cAMP, dibutyryl-guanosine 3'5'-cyclic monophosphate, staurosporine, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine did not affect either the control HVA IBa or the SS-induced inhibition of HVA IBa. 5. Pretreatment with protein kinase C (PKC) activators had no significant effect on HVA IBa but did remove the inhibition of HVA IBa by SS. 6. Omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked HVA IBa by 27, 13, 38, and 9% of the total HVA current, respectively, which suggested the existence of N-, P-, L-, and Q-type HVA Ca2+ channels in the hippocampal CA1 pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin modulates high-voltage-activated Ca2+ channels in freshly dissociated rat hippocampal neurons. 750 Jan 29

Voltage-dependent calcium currents were measured by whole-cell recording technique in cultured cerebellar granule neurons from 8 d old rats, in 10 mM BaCl2 and with a holding potential of -80 mV. A saturating dose (10 microM) of the dihydropyridine nimodipine reversibly inhibited the maximum current by 25% and the dose dependence showed IC50 close to 50 nM. omega-Conotoxin GVIA (cgtx, 5 microM) and omega-agatoxin IVA (agatx, 200 nM) irreversibly inhibited the current by 17% and by 47%, respectively. The effect of nimodipine was additive with that of the toxins. The GABAB agonist (+/-)baclofen, or (-)baclofen (100 microM), reduced the calcium current by 30 +/- 5%, with a IC50 4 microM. The effect was mediated by a pertussis toxin-sensitive G-protein. In cells treated with cgtx during the experiment or preincubated with the toxin for 30 min, the effect of baclofen was significantly reduced. However, the action of baclofen was not confined to cgtx-sensitive channels: application of nimodipine or agatx resulted in a 50% reduction of the baclofen effect as well. In contrast, baclofen inhibited approximately the same amount of current both before and after the increase caused by the dihydropyridine agonist BayK 8644 and did not modify the slow BayK-induced tail current. These results indicate (1) the modulation through GABAB receptors does not clearly discriminate between pharmacologically distinct calcium channels and (2) L-type calcium channels represent an heterogeneous population in these neurons.
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PMID:Pharmacological types of calcium channels and their modulation by baclofen in cerebellar granules. 753 21

Neuropeptide Y (NPY) is a widely distributed peptide with varied activities including inhibition of [3H]NE secretion from chromaffin cells. In the present study, we investigated the mechanism through which NPY and NPY fragments inhibit nicotinic receptor induced influx of 22Na+ and 45Ca++ into bovine chromaffin cells. Fragments of NPY, including NPY13-36, NPY18-36 and NPY26-36, are more potent inhibitors of 45Ca++ and 22Na+ influx than NPY. High [K+]- and BAY K 8644-induced 45Ca++ influx and veratridine-induced 22Na+ influx are not inhibited by either NPY or NPY fragments. Thus, the site of NPY or NPY fragment action is not voltage-gated Ca++ or Na+ channels. A significant amount of acetylcholine-induced 45Ca++ influx still occurs in the presence of the voltage-gated Ca++ channel blockers: nifedipine (L-type), omega-conotoxin-GVIA (N-type) and omega-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY 18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 > or = NPY26-36 > NPY13-36 > NPY13-36 > NPY > or = NPYfree acid. Moreover, the IC50 values for NPY18-36 inhibition of 45Ca++ influx and 22Na+ influx are similar, 0.9 x 10(-6) M and 2.03 x 10(-6) M, respectively. Regression analysis for inhibition of these two phenomena produced a correlation coefficient of .9697 (P < .0003).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel. 754 75

1. Modulation of Ca(2+)-channel currents by phorbol-12-myristate-13-acetate (PMA) was investigated in acutely dissociated adult rat superior cervical ganglion neurons using the whole cell variant of the patch-clamp technique. 2. PMA (500 nM) increased the current amplitudes, accelerated the inactivation of step currents, retarded the deactivation of tail currents, and shifted the tail current activation to more negative potentials. 3. The effects of PMA were concentration and voltage dependent and mediated through activation of protein kinase C (PKC). PMA also increased Ca2+ currents recorded with the perforated patch technique. 4. PMA affected the N-type Ca2+ channels and an omega-conotoxin GVIA-resistant current component. Ca2+ currents affected by PMA were not sensitive to omega-agatoxin IVA or nimodipine. 5. PMA not only attenuated Ca(2+)-channel inhibition induced by alpha 2-adrenoceptor agonist, which modulates Ca2+ channels via a pertussis toxin (PTX)-sensitive pathway, but also attenuated current inhibition by vasoactive intestinal polypeptide, which modulates Ca2+ channels via a PTX-insensitive but cholera toxin-sensitive pathway. 6. PMA reversed Ca(2+)-channel inhibition induced by tonic activation of G-protein in the absence of neurotransmitter (even in neurons pretreated with PTX) or induced by activation of G-proteins with guanosine 5'-O-(3-thiotriphosphate) (GTP)-gamma-S. 7. Inhibition of phosphatase by okadaic acid or substitution of Ba2+ for Ca2+ in the external solutions accelerated the PMA effect. 8. Our results suggest that activation of PKC antagonizes G-protein mediated inhibition of Ca2+ channels by shifting Ca2+ channels from the "reluctant" state to the "willing" state. The G-proteins and, more likely, the N-type Ca2+ channels may be the target of PKC phosphorylation. Protein phosphatases may be involved in counteracting the PKC phosphorylation in rat sympathetic neurons.
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PMID:Modulation of Ca(2+)-channel currents by protein kinase C in adult rat sympathetic neurons. 782 85

1. Ca(2+)-channel modulation by adenosine was investigated in enzymatically dispersed adult rat superior cervical ganglion (SCG) neurons using the whole-cell variant of the patch-clamp technique. 2. Adenosine produced a concentration-dependent decrease in the Ca(2+)-current amplitude with an EC50 of 174 nM and maximum inhibition of 36%. The effects of adenosine on the Ca2+ current were both time and voltage dependent. The inhibition was maximal at +10 mV and decreased at either hyperpolarizing or depolarizing potentials. 3. The inhibitory response desensitized after prolonged (> 1 min) exposure to 10 microM adenosine, whereas multiple brief (< 30 s) applications slightly decreased the subsequent response. 4. Adenosine-induced Ca2+ current inhibition was mediated by an A1-type adenosine receptor, because the half-maximal inhibition value for an A1 receptor selective agonist, chloro-N-cyclopentyladenosine, was 1,000-fold lower than that for an A2 receptor selective agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarbozamido adenosine hydrochloride (33 nM vs. 40 microM, respectively). 5. A guanine nucleotide binding protein (G protein) appeared to be involved in the action of adenosine, because: 1) the adenosine-induced current inhibition could be largely relieved by depolarizing voltage prepulses; 2) tail current analysis revealed that adenosine shifted Ca(2+)-channel activation to more depolarized potentials; and 3) adenosine inhibition was abolished by 2 mM intracellular guanosine 5'-O-(2-thiodiphosphate) or 500 ng/ml pertussis toxin pretreatment. 6. Adenosine did not appear to inhibit L-type Ca2+ channels, because the prolonged tail current component induced by the dihydropyridine "agonist" 2,6-dimethy-3-carbomethoxy-5-nitro-4-(2-trifluoromethyl-phenyl)- 1,4-dihydropyridine (2 microM) was not affected by adenosine. 7. Adenosine-induced inhibition was reduced to approximately 15% after application of 10 microM omega-conotoxin GVIA, suggesting that adenosine primarily inhibits N-type Ca2+ channels. The Ca(2+)-current component resistant to omega-conotoxin GVIA was also resistant to omega-agatoxin IVA (200 nM), suggesting a lack of P-type of Ca2+ channels in SCG neurons. 8. In conclusion, adenosine produces a dose-, time-, and voltage-dependent inhibition of Ca2+ currents in SCG neurons. Adenosine acts on an A1 adenosine receptor subtype in SCG neurons via a pertussis toxin-sensitive G protein to inhibit N-type Ca2+ channels and an unidentified Ca(2+)-current component. Modulation of Ca2+ currents by adenosine may be an important mechanism for its inhibitory effect on neurotransmitter release in sympathetic neurons.
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PMID:Adenosine modulates voltage-gated Ca2+ channels in adult rat sympathetic neurons. 841 Jan 61

The effects of norepinephrine on the low- and high-voltage-activated calcium channels in the neurons acutely dissociated from the nucleus tractus solitarius of 2- to 3-week-old rats were investigated in the nystatin perforated patch recording configuration under voltage-clamp conditions. The norepinephrine had no effect on the low voltage-activated calcium channel but inhibited the high voltage-activated calcium channel in a concentration-, time- and voltage-dependent manner. The norepinephrine slowed the activation phase of the high voltage-activated calcium channel current and the maximum inhibition was 30% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. The pretreatment with pertussis toxin completely blocked the norepinephrine effect on high-voltage activated calcium channels, suggesting the contribution of pertussis toxin-sensitive Gi/Go-proteins to the norepinephrine-induced inhibition. Yohimbine but not prazosin nor propranolol antagonized the norepinephrine-induced inhibition, suggesting the involvement of alpha 2-adrenoceptor in norepinephrine-induced inhibition of the high voltage-activated calcium channels. omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine and omega-conotoxin-MVIIC blocked the high voltage-activated calcium channel current by 26, 9, 36 and 11% of the total current respectively, suggesting the existence of N-, P-, L- and Q-type calcium channels in the nucleus tractus solitarii neurons. The current being insensitive to these calcium channel antagonists, termed R-type calcium channel current, also existed. This residual R-type calcium channel was completely blocked by adding 200 microM CD2+. The norepinephrine significantly inhibited N- and P-type calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Norepinephrine modulates high voltage-activated calcium channels in freshly dissociated rat nucleus tractus solitarii neurons. 854 88

Metabotropic glutamate receptor (mGluR) modulation of voltage-gated Ca2+ channels was examined in isolated deep layer frontoparietal cortical neurons under conditions designed to isolate calcium-independent modulatory pathways. Trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD), a nonspecific mGluR agonist, produced rapid and reversible inhibition of Ca2+ channels. This effect was mimicked by agonists for group I and group II, but not group III, mGluRs. Effects of group I and II agonists often were observed in the same neurons, but separate subgroups of neurons were unresponsive to the group I agonist quisqualate or the group II agonist 2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV). Inhibition by quisqualate and DCG-IV was nonocclusive in neurons responding to both agonists. These agonists thus appear to act on different mGluRs. The mGluR antagonist alpha-methyl-4-carboxylphenylglycine attenuated inhibition by t-ACPD, quisqualate, and DCG-IV. Inhibition by quisqualate and DCG-IV was voltage-dependent. Although the effects of both agonists were greatly reduced by N-ethylmaleimide (NEM), inhibition by DCG-IV was more sensitive to NEM than inhibition by quisqualate. t-ACPD-induced inhibition was reduced by omega-conotoxin GVIA (omega-CgTx) and omega-agatoxin IVA (omega-AgTx) but was affected little by nifedipine. Inhibition by DCG-IV and quisqualate also was reduced by omega-CgTx. We conclude that multiple mGluR subtypes inhibit Ca2+ channels in cortical neurons and that N- and possibly P-type channels are inhibited. Modulation is via a rapid-onset, voltage-dependent mechanism that likely involves a pertussis toxin (PTX)-sensitive G-protein. Type I mGluRs may work via additional PTX-insensitive pathways.
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PMID:Metabotropic glutamate receptor modulation of voltage-gated Ca2+ channels involves multiple receptor subtypes in cortical neurons. 861 3

1. Whole-cell Ca2+ currents (ICa) from cultured rat melanotrophs were identified by their sensitivity to Ca2+ channel blockers, and their modulation by serotonin (5-HT) was studied. All cells displayed high voltage-activated (HVA; > -30 mV) Ca2+ currents. A low voltage-activated (LVA; > -60 mV) Ca2+ current was detected in 92% of the cells. 2. The whole-cell ICa was insensitive to omega-conotoxin GVIA (0.5-1 microM) indicating the absence of N-type Ca2+ channels. 3. At a holding potential (Vh) of -70 mV, the L-type channel blocker nifedipine reduced ICa in a dose-dependent manner with a half-maximal effective concentration (IC50) of 28 nM. The L-type current represented 39% of the total ICa. 4. omega-Agatoxin IVA (omega-Aga IVA) produced a biphasic dose-dependent inhibition of ICa, with IC50 values of 0.4 and 91 nM, indicating the presence of P-type and Q-type Ca2+ channels, which accounted respectively for 16 and 45% of the total ICa. The P-type current was also blocked by synthetic funnel-web spider toxin (sFTX 3.3; 1-10 microM) and was present only in a subpopulation (60-70%) of cells. 5. All cells possessed a Ca2+ current which was resistant to nifedipine (10 microM) and omega-Aga IVA (50 nM). This current was not affected by Ni2+ (40 microM) but was abolished by a low concentration of Cd2+ (10 microM) and by omega-conotoxin MVIIC (1 microM) indicating that it was a Q-type Ca2+ current. 6. 5-HT (10 microM) inhibited the whole-cell ICa in 70% of the cells tested (n = 120) by activating 5-HT1A and 5-HT2C receptors. 5-HT produced either a kinetic slowing of the activation phase (37% of the cells) or a scaling down (14% of the cells) of ICa. In the majority of cells (49%) both types of inhibition were found to coexist. 7. The effects of 5-HT were voltage dependent, rendered irreversible when GTP-gamma-S (30 microM) was present in the pipette solution and abolished by pretreatment of the cells with pertussis toxin (PTX; 150 ng ml-1, 18 h). 8. Low concentrations of omega-Aga IVA (20 nM), which blocked mainly P-type channels, did not reduce the effect of 5-HT on ICa. The scaling down effect of 5-HT on ICa was eliminated in the presence of nifedipine (10 microM) and the kinetic slowing effect of 5-HT persisted after blockade of L- and P-type channels but was abolished by omega-conotoxin MVIIC (1 microM). 9. We conclude that rat melanotrophs possess functional L-, P- and Q-type Ca2+ channels and that 5-HT inhibits selectively L-type and Q-type Ca2+ currents with different modalities. These effects are voltage dependent and mediated by a PTX-sensitive G-protein.
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PMID:Selective inhibition of high voltage-activated L-type and Q-type Ca2+ currents by serotonin in rat melanotrophs. 868 60

In this study we determined the changes in the intracellular free Ca2+ concentration, associated with the inhibitory modulation of the exocytotic release of GABA by GABAB receptor activation in rat cerebrocortical synaptosomes. We observed that SK&F 97541 and (-)baclofen both act as agonists of the presynaptic GABAB receptors in modulating GABA release and Ca2+ influx due to KCl (10 mM) depolarization, but SK&F 97541 is more potent than (-)baclofen in modulating both Ca2+ influx and GABA release. Thus, activation of GABAB receptors by either SK&F97541 (10 microM) or by (-)baclofen (100 microM) caused about 18% inhibition of the increase in [Ca2+]i, due to KCl depolarization, and inhibited the [3H]GABA release by about 30%. The pharmacological similarities of the GABAB receptor activation in producing inhibition of both calcium channel mediated influx of Ca2+ and transmitter release suggest that presynaptic inhibition of GABA release by GABAB receptor activation may result, at least in part, from inhibition of Ca2+ influx through P-type (or possibly Q-type) Ca2+ channels, sensitive to omega-Agatoxin IVA (200 nM). Furthermore, modulation of GABA release of GABAB receptors was abolished by preincubation with pertussis toxin, suggesting that a pertussis toxin sensitive G protein may be the coupling factor between GABAB receptors and the voltage-dependent Ca2+ channels associated with the exocytotic release of GABA in rat cerebrocortical nerve terminals.
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PMID:Regulation of intracellular [Ca2+] and GABA release by presynaptic GABAB receptors in rat cerebrocortical synaptosomes. 884 40

Involvement of P-type voltage-dependent Ca2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, omega-agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5-6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of omega-agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, omega-agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, omega-agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.
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PMID:Omega-agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism. 895 49

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