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)

1. The effect of acetylcholine (ACh) on voltage-dependent Ca2+ currents in mouse pancreatic B-cells was studied using the whole-cell configuration of the patch-clamp technique. 2. ACh (0.25-250 microM) reversibly and dose-dependently inhibited the Ca2+ current elicited by depolarizations from -80 mV to +10 mV. Maximal inhibition was observed at concentrations > 25 microM where it amounted to approximately 35%. The effect was voltage independent and prevented by atropine (10 microM) suggesting that it was mediated by muscarinic receptors. 3. The inhibitory action of ACh on the Ca2+ current was abolished when the cytoplasmic solution contained GDP beta S (2 mM) and became irreversible when the non-hydrolysable GTP analogue GTP gamma S (10 microM) was included in the pipette. This indicates the participation of G proteins in the inhibitory effect of ACh but pretreatment of the cells with either pertussis or cholera toxin failed to prevent the effect of ACh on the Ca2+ current. 4. ACh remained equally effective as an inhibitor of the whole-cell Ca2+ current in the presence of the L-type Ca2+ channel agonist (-)-Bay K 8644 and after partial inhibition of the current by nifedipine. Addition of omega-agatoxin IVA, omega-conotoxin GVIA or omega-conotoxin MVIIC neither affected the peak Ca2+ current amplitude nor the extent of inhibition produced by ACh. These pharmacological properties indicate that ACh acts by inhibiting L-type Ca2+ channels. 5. The inhibitory action of ACh on the B-cell Ca2+ current was not secondary to elevation of [Ca2+]i and ACh remained equally effective as an inhibitor when Ba2+ was used as the charge carrier, when [Ca2+]i was buffered to low concentrations using EGTA and under experimental conditions preventing the mobilization of Ca2+ from intracellular stores. 6. These results suggest that ACh reduces the whole-cell Ca2+ current in the B-cell through a G protein-regulated, voltage- and Ca(2+)-independent inhibition of L-type Ca2+ channels.
 ...
PMID:G protein-dependent inhibition of L-type Ca2+ currents by acetylcholine in mouse pancreatic B-cells. 906 40

We characterized whole cell barium currents through calcium channels and investigated the effects of serotonin (5-HT) on calcium channel currents and firing behavior in visualized caudal raphe neurons of the neonatal rat in brain stem slices (n = 201). A subpopulation of recorded neurons was recovered after staining for tryptophan hydroxylase (TPH), the 5-HT synthesizing enzyme (n = 21); of those cells, 86% were TPH immunoreactive, suggesting that the majority of recorded neurons was serotonergic. Calcium channel currents began to activate at about -40 mV in caudal raphe neurons and showed a peak amplitude of 952.2 +/- 144.2 (SE) pA at -10 mV. A small low-voltage activated current was also observed (approximately 22 pA). Calcium channel currents were potently inhibited by bath-applied 5-HT in most cells tested (approximately 90%). The EC50 for inhibition of calcium current by 5-HT was 0.1 microM; a saturating concentration (1.0 microM) blocked approximately 40% of the current evoked at 0 mV from a holding potential of -70 mV (n = 101). Current inhibition was associated with a slowing of activation kinetics and a shift in the peak of the current-voltage relationship, and was partially relieved by strong depolarizations. Current inhibition by 5-HT was mimicked by 8-OH-DPAT, a specific 5-HT1A agonist, and blocked by the 5-HT1a antagonists NAN 190 and (+) WAY 100135, but was unaffected by ketanserin, a 5-HT2A/C antagonist. omega-Conotoxin GVIA (omega-CgTx)-sensitive N-type channels and omega-agatoxin IVA (omega-AgaIVA)-sensitive P/Q-type channels together accounted for most of the calcium current (36 and 37%, respectively). Nimodipine had no effect on the calcium current, indicating that caudal raphe neurons do not express dihydropyridine-sensitive L-type currents. A substantial residual current (27%) remained after application of omega-CgTx, omega-AgaIVA, and nimodipine. Most of the 5-HT-sensitive calcium current was blocked by omega-CgTx and omega-AgaIVA; 5-HT had little effect on the residual current. Inhibition of calcium current by 5-HT was irreversible when GTP gamma S, a nonhydrolyzable guanosine 5'-triphosphate (GTP) analogue, was substituted for GTP in the pipette. In addition, the effects of 5-HT were blocked by pretreating slices with pertussis toxin (PTX). Together these data indicate that inhibition of N- and P/Q-type calcium current in serotonergic caudal raphe neurons is mediated by a 5-HT1A receptor via PTX-sensitive G proteins. Under current clamp, calcium channel toxins (omega-CgTx and omega-AgaIVA) and 5-HT each caused a decrease in the spike afterhyperpolarization and enhanced the repetitive firing response to injected current. The similar effects of 5-HT and the calcium channel toxins on firing behavior suggest that those effects of 5-HT were secondary to inhibition of N- and P/Q-type calcium channels.
 ...
PMID:Effects of serotonin on caudal raphe neurons: inhibition of N- and P/Q-type calcium channels and the afterhyperpolarization. 908 3

The modulation of high-voltage-activated (HVA) Ca2+ channels by serotonin (5-HT) was studied in ventromedial hypothalamic (VMH) neurons acutely dissociated from 12-14-day-old Wistar rats using the whole-cell and nystatin perforated-patch recording configurations. 5-HT inhibited the HVA Ca2+ channels in a concentration-, time- and voltage-dependent manner. This inhibition was mimicked by the 5-HT1A agonist 8-hydroxy-dipropylaminotetralin and was prevented by pretreatment with pertussis toxin (PTX). omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine and omega-conotoxin-MVIIC blocked each fraction of HVA Ca2+ channel currents, suggesting the existence of N-, P-, L- and Q-types of HVA Ca2+ channels. A component of the current resistant to these Ca2+ channel antagonists also existed in the VMH neurons. Among these five components of HVA Ca2+ channel currents, the N- and Q-type currents were significantly inhibited by 5-HT. These findings suggest that the activation of 5-HT1A receptors produces the selective inhibition of N- and Q-type Ca2+ channels through a PTX-sensitive G-protein in rat VMH neurons.
 ...
PMID:Serotonin modulates high-voltage-activated Ca2+ channels in rat ventromedial hypothalamic neurons. 912 12

1. The present report gives a detailed account of histamine-stimulated phospholipase C (PLC) activity in bovine adrenal chromaffin cells. 2. Histamine activation of H1 receptors stimulates PLC with a biphasic sensitivity to extracellular Ca2+. The initial response (the first 15 s stimulation) was not reduced by the removal of extracellular Ca2+, whereas the maintenance of PLC activity beyond this time required Ca2+ influx. 3. Phospholipase C activity in response to a 10 min incubation with histamine was inhibited by La3+ (3 mmol/L) or SKF96365 (10 mumol/L). Nifedipine (10 mumol/L), but not omega-agatoxin IVA (100 nmol/L) or omega-conotoxin GVIA (300 nmol/L), produced a partial inhibition of PLC activity. The response was also partially inhibited by a reduction in the extracellular Cl- concentration (40 mmol/L) or by the inclusion of the Cl- channel blocker N-phenylanthranilic acid (300 mumol/L). 4. Kinetic analysis of the rate of turnover of the various inositol phosphate isomers in response to histamine suggested that the inositol monophosphates were being produced from a source in addition to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) metabolism. This conclusion was supported by the differential action of pertussis toxin and neomycin on Ins(1,4,5)P3 formation compared with inositol monophosphate formation. 5. We have attempted to identify a defined role for the intracellular Ca2+ mobilized in these cells in response to histamine. After short incubations (up to 3 min), histamine was able to regulate the site-specific phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This observation has important implications for a possible role for the PLC signalling pathway in controlling the rate of catecholamine biosynthesis.
 ...
PMID:Histamine-stimulated phospholipase C signalling in the adrenal chromaffin cell: effects on inositol phospholipid metabolism and tyrosine hydroxylase phosphorylation. 926 39

Inhibition of Ca2+ currents by the excitatory neurotransmitters neurotensin and substance P was investigated in cultured nucleus basalis neurons with the use of the whole cell patch-clamp technique. The whole cell Ca2+ current, elicited from a holding potential of -80 mV by a step pulse to 0 mV and measured at 100 ms, was inhibited 67.9% by neurotensin and 57.6% by substance P. Low-voltage-activated (LVA) Ca2+ current, elicited by a step pulse to -40 mV from a holding potential of -90 mV, was inhibited by both neurotensin (26.2%) and substance P (24.1%). High-voltage-activated Ca2+ currents were separated with the use of the Ca2+ channel antagonists. Nimodipine (3 microM) inhibited 24.2% of the whole cell Ca2+ current elicited by a step to 0 or +10 mV and measured at 100 ms. Under the same conditions, omega-conotoxin (omega-CgTx)-GVIA (0.5 microM) inhibited 46.4%, omega-CgTx-GVIA + nimodipine 58.7%, and omega-CgTx-MVIIC (5 microM) + nimodipine 75.7% of the current. Omega-Agatoxin (omega-Aga)-IVA (100 nM) did not produce any effect. Neurotensin inhibition of the whole cell Ca2+ current was attenuated by each of these treatments except for the omega-Aga-IVA treatment, which did not change the neurotensin effect. In contrast, neither the omega-Aga-IVA nor the nimodipine treatment had any effect on the substance-P-induced inhibition; the rest of the treatments attenuated the substance-P-induced response. Thus the data indicate that nucleus basalis neurons express LVA as well as L-, N-, and Q-type, but not the P-type, Ca2+ currents. N- and Q-type HVA Ca2+ currents, as well as LVA Ca2+ currents, are inhibited by both neurotensin and substance P. In contrast, L-type current is inhibited by neurotensin but not by substance P. In addition, a fraction of the total whole cell current was resistant to all Ca2+ channel antagonists and thus may correspond to the R-type Ca2+ current. This residual current was inhibited by both neurotensin and substance P. The inhibition of the whole cell Ca2+ current produced by both neurotransmitters was voltage independent, because a large depolarization (+70 mV) was not able to relieve either effect. In cells loaded with 0.1 mM guanosine 5'-[gamma-thio]triphosphate, response to both neurotensin and substance P became irreversible, indicating that the effects of both neurotransmitters were mediated through G proteins. However, pertussis toxin did not affect either the neurotensin or the substance P response.
 ...
PMID:Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+ channels in cultured newborn rat nucleus basalis neurons. 931 Apr 25

With use of the whole cell patch-clamp technique, effects of the potent muscarinic agonist oxotremorine methiodide (oxo-M) on voltage-activated Ca2+ channel currents were investigated in acutely dissociated adult rat intracardiac neurons. In all tested neurons oxo-M reversibly inhibited the peak Ba2+ current. Inhibition of the peak Ba2+ current by oxo-M was associated with slowing of activation kinetics and was concentration dependent. The concentration of oxo-M necessary to produce a half-maximal inhibition of current and the maximal inhibition were 40.8 nM and 75.9%, respectively. Inhibitory effect of oxo-M was completely abolished by atropine. Among different muscarinic receptor antagonists, methoctramine (100 and 300 nM) significantly antagonized the current inhibition by oxo-M, with a negative logarithm of dissociation constant of 8.3 in adult rat intracardiac neurons. Internal dialysis of neurons with guanosine 5'-(thio)triphosphate (GTPgammaS, 0.5 mM) could mimic the muscarinic inhibition of the peak Ba2+ current and significantly occlude inhibitory effects of oxo-M. In addition, the internal dialysis of guanosine-5'-O-(2-thiodiphosphate) (GDPbetaS, 2 mM) also significantly reduced the muscarinic inhibition of the peak Ba2+ current by oxo-M. Inhibitory effects of oxo-M were significantly abolished by pertussis toxin (PTX, 200 and 400 ng/ml) but not by cholera toxin (400 ng/ml). Furthermore, the bath application of N-ethylmaleimide (50 microM) significantly reduced the inhibition of the peak Ba2+ current by oxo-M. The oxo-M shifted the activation curve derived from measurments of tail currents toward more positive potentials. A strong conditioning prepulse to +100 mV significantly relieved the muscarinic inhibition of peak Ba2+ currents by oxo-M and the GTPgammaS-induced current inhibition. In a series of experiments, changes in intracellular concentration of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid and protein kinase activities failed to mimic or occlude the current inhibition by oxo-M. The dihydropyridine antagonist nifedipine (10 microM) was not able to occlude any of the inhibitory effects of oxo-M, and oxo-M (3 microM) failed to reduce the slow tail currents induced by the L-type agonist methyl 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate (FPL 64176; 2 microM). However, omega-conotoxin (omega-CgTX) GVIA (1 microM) significantly occluded the muscarinic inhibition of the Ba2+ currents. In the presence of omega-CgTX GVIA (1 microM) and nifedipine (10 microM), oxo-M could further inhibit approximately 20% of the total Ca2+ current. After complete removal of N-, Q-, and L-type currents with use of omega-CgTX GVIA, omega-agatoxin IVA, and nifedipine, 70% of the R-type current (approximately 6-7% of the total current) was inhibited by oxo-M (3 microM). In conclusion, the M2 muscarinic receptor activation selectively inhibits N-, Q-, and R-type Ca2+ channel currents, sparing L-type Ca2+ channel currents mainly via a PTX- and voltage-sensitive pathway in adult rat intracardiac neurons.
 ...
PMID:Muscarinic receptor activation modulates Ca2+ channels in rat intracardiac neurons via a PTX- and voltage-sensitive pathway. 931 Apr 37

Presynaptic adenosine receptors inhibit transmitter release at many synapses and are known to exist on retinotectal terminals. In this paper we show that adenosine decreases retinotectal field potentials by approximately 30% and investigate the mechanism. First, as judged by the effects of specific calcium channel blockers, retinotectal transmission was mediated almost exclusively by N-type calcium channels, which are known to be modulated by adenosine A1 receptors. Transmission was completely blocked by either omega-Conotoxin GVIA (-100%, N-type blocker) or omega-Conotoxin MVIIC (-99%, N-, P- and Q-type blocker) and was not significantly affected by omega-Agatoxin IVA [+1.7 +/- 9. 3% (SE), P-,Q-type blocker], but was augmented slightly by nifedipine(+9.3 +/- 2.1%, L-type blocker). Second, the adenosine inhibition was presynaptic, as indicated by a 43% increase in paired-pulse facilitation. Third, the selective A1 agonist cyclohexyl adenosine (CHA) at 50 nM caused a 21% decrease in amplitude and the selective A2 agonist N6-[2-(3, 5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) at 100 nM caused a 24% increase. Fourth, the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) alone produced an increase in the field potential, suggesting a tonic inhibition mediated by endogenous adenosine. Fifth, pertussis toxin eliminated adenosine inhibition implicating Gi or Go protein coupling. Sixth, C-kinase activation eliminated the A1-mediated inhibition. In regenerating projections, adenosine also caused a decrease in transmission (-30 +/- 12%), but after induction of long-term potentiation (LTP) via trains of stimuli or via treatment with the phosphatase inhibitor okadaic acid, the adenosine response was converted to an augmentation. Because LTP is associated with C-kinase activation, this is consistent with C-kinase uncoupling the A1 receptor from inhibiting N-type Ca2+ channels. This uncovers the A2-mediated augmentation as demonstrated in normals with DPMA. Such an effect could account in part for the LTP of immature synapses and the change from rapidly fatiguing to robust synaptic transmission.
 ...
PMID:Adenosine A1 receptors mediate retinotectal presynaptic inhibition: uncoupling by C-kinase and role in LTP during regeneration. 946 17

Many neurotransmitter receptors that interact with pertussis toxin-sensitive G proteins, including the alpha 2-adrenergic receptor, can modulate both voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels. Serotonergic neurons of the medulla oblongata (nucleus raphe obscurus and nucleus raphe pallidus), which provide a major projection to sympathetic and motor output systems, receive a catecholaminergic input and express alpha 2-adrenergic receptors. Therefore, we tested the effects of norepinephrine on voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels in neonatal raphe neurons using whole-cell recording in a brainstem slice preparation. Calcium channel currents were inhibited by norepinephrine in the majority of raphe neurons tested (88%) and in all identified tryptophan hydroxylase-immunoreactive (i.e. serotonergic) neurons. When tested in the same neurons, the magnitude of calcium current inhibition by norepinephrine (approximately 25%) was less than that induced by 5-hydroxytryptamine (approximately 50%). The norepinephrine-induced calcium current inhibition was mediated by alpha 2-adrenergic receptors; it was mimicked by UK 14304, an alpha 2-adrenergic receptor agonist and blocked by idazoxan, an alpha 2-adrenergic receptor antagonist, but not affected by prazosin or propanolol (alpha 1 and beta adrenergic antagonists, respectively). Calcium current inhibition by norepinephrine was essentially eliminated following application of omega-Conotoxin GVIA and omega-Agatoxin IVA, indicating that norepinephrine modulated N- and P/Q-type calcium channels predominantly. Calcium current inhibition by norepinephrine was voltage-dependent and mediated by pertussis toxin-sensitive G proteins. Thus, as expected, alpha 2-adrenergic receptor activation inhibited N- and P/Q-type calcium currents in medullary raphe neurons via pertussis toxin-sensitive G proteins. In parallel experiments, however, we found that norepinephrine had no effect on G protein-coupled inwardly-rectifying K+ channels in any raphe neurons tested, despite the robust activation of those channels in the same neurons by 5-hydroxytryptamine. Together, these data indicate that alpha 2-adrenergic receptors can modulate N- and P/Q-type calcium channels in caudal medullary raphe neurons but do not couple to the G protein-coupled inwardly-rectifying K+ channels which are also present in those cells. This is in contrast to the effect of 5-hydroxytryptamine1A receptor activation in caudal raphe neurons, and indicates a degree of specificity in the signalling by different pertussis toxin-sensitive G protein-coupled receptors to voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels even within the same cell system.
 ...
PMID:Activation of alpha 2-adrenoceptors causes inhibition of calcium channels but does not modulate inwardly-rectifying K+ channels in caudal raphe neurons. 948 33

1. The actions of the neuropeptide nociceptin on the calcium channel currents (IBa) of acutely dissociated rat periaqueductal grey (PAG) neurons were examined using whole-cell patch clamp techniques. These effects were compared with those of opioid receptor agonists and the GABAB receptor agonist baclofen. 2. Neurons from young adult rats (23 to 56 days old) expressed predominantly omega-conotoxin GVIA (N-type)- and omega-agatoxin IVA (P/Q-type)-sensitive IBa, together with smaller amounts of nimodipine-sensitive current and current resistant to all three blockers. There was proportionately more N-type IBa in neurons from female rats and proportionately more resistant current in neurons from male rats. 3. Nociceptin (EC50, 5 nM) and baclofen (EC50, 0.8 microM) inhibited IBa in all PAG neurons, while the opioid agonist methionine enkephalin (met-enkephalin; 300 nM-10 microM) inhibited IBa in 40 % of neurons. The effects of met-enkephalin were reversed by the mu-opioid antagonist CTAP, and mimicked by the mu-opioid agonist DAMGO (300 nM-3 microM). The delta-opioid agonists DPDPE and deltorphin II, and the kappa-opioid agonist U69593, did not affect IBa in any neuron. The actions of nociceptin were not mimicked or blocked by the opioid antagonist naloxone or the nociceptin analogue [desPhe1]-nociceptin. 4. The effects of nociceptin and baclofen on IBa were blocked by pretreatment of the neurons with pertussis toxin (500 ng ml-1, 8 h). 5. Nociceptin predominantly inhibited the N-type (EC50, 2 nM; maximum inhibition, 50 %) and P/Q-type (EC50, 7 nM; maximum inhibition, 33 %) IBa while having little effect on the L-type and R-type IBa. 6. These results are consistent with the previously described actions of nociceptin, baclofen and micro-opioids in PAG slices, whereby they couple to increases in an inwardly rectifying K+ conductance. These agonists thus have the potential to modulate the function of PAG neurons via a number of different cellular effectors.
 ...
PMID:Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons. 954 80

The effects of histamine on high-voltage-activated Ca2+ channels in the histaminergic neurons acutely dissociated from the rat tuberomammillary nucleus were investigated in the nystatin-perforated patch recording mode under voltage-clamp conditions. Histamine suppressed the high-voltage-activated Ca2+ channel currents in neurons which were positive for histidine decarboxylase with immunocytochemistry. The half-maximum inhibitory concentration and maximum inhibition were 2.6 x 10(-7) M and 16.6+/-1.90%, respectively. An H3 receptor agonist, R(-)-alpha-methylhistamine, mimicked the response to histamine, and thioperamide, an H3 receptor antagonist, inhibited the response to histamine. On the other hand, neither 2-methylhistamine, an H1 receptor agonist, nor dimaprit, an H2 receptor agonist, had a significant effect on the Ca2+ channel currents. Pretreatment with pertussis toxin blocked the inhibitory effect of histamine on Ca2+ channels, suggesting the involvement of Gi/Go proteins in the action of histamine. Omega-conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked the high-voltage-activated Ca2+ channel currents by 15.6, 4.3, 27.1, and 31.2% of the total current, respectively, suggesting the existence of N-, P-, L-, and Q-type Ca2+ channels. A current that was insensitive to these blockers was also found. This residual current, "R-type", was completely suppressed by the addition of 200 microM Cd2+. Histamine significantly inhibited both the N- and P-type current components among these five types of Ca2+ channel currents. We concluded that histamine suppresses the N- and P-type Ca2+ channels in histaminergic neurons through an H3 receptor which is linked to a pertussis toxin-sensitive G-protein.
 ...
PMID:Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus. 975 67


<< Previous 1 2 3 Next >>