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

L-type Ca2+ current (ICa) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of ICa induced by beta-adrenergic stimulation (isoprenaline 2.10(-7) M) could be completely antagonized by diluted sera (1:100 v/v). Half-maximal inhibition of beta-receptor-stimulated ICa occurred at about 1:1000. Basal ICa was not affected by serum. Atropine in a concentration (10(-6) M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2.10(-6) M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10(-4) M) pipette solution, potentiated ICa was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits beta-receptor-stimulated adenylyl cyclase via Gi-protein.
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PMID:Serum contains a potent factor that decreases beta-adrenergic receptor-stimulated L-type Ca2+ current in cardiac myocytes. 839 81

The possible role of altered humoral immunity in cardiac Chagas' disease was examined by analyzing the interaction of IgG and the corresponding F(ab')2 from Trypanosoma cruzi-infected patients with cardiac muscarinic cholinergic receptors (mAchR). Human chagasic IgG and its F(ab')2 simulated the agonist actions triggering the biological effects associated with cholinergic-mediated cellular transmembrane signals, i.e. stimulation of cGMP, inhibition of cAMP and a decrease in atrial contractility. Atropine blunted all of these effects while pertussis toxin prevented the inhibition of cAMP and contractility confirming the G-regulatory-protein-mediated response in the interaction of chagasic antibodies with cardiac mAchR. In addition, chagasic IgG and its F(ab')2 behaved as partial agonists activating the specific receptor and inhibiting in a noncompetitive manner the activity of an exogenous agonist (pilocarpine). Moreover, chagasic IgG immunoprecipitated the mAchR solubilized from cardiac membrane in a concentration-dependent fashion. By means of SDS-PAGE and immunoblotting analysis, chagasic serum was shown to recognize a band of approximately 75 kD. The electrophoretic studies of prelabeled immunoprecipitated proteins revealed a peak of [3H] propylbenzilylcholine mustard with an apparent molecular weight similar to that of mAchR, which disappeared in the presence of atropine. The presence of these antibodies in the serum of chagasic patients could explain the progressive receptor blockade in the parasympathetic branch of the cardiac autonomic nervous system associated with the cardioneuromyopathy described in the course of Chagas' disease.
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PMID:Modification of cholinergic-mediated cellular transmembrane signals by the interaction of human chagasic IgG with cardiac muscarinic receptors. 852 94

1. In the present study, we examined the cellular mechanism and receptor type responsible for a muscarine-induced inward current (Imi) in neurons of rat dorsolateral septal nucleus (DLSN) using single-microelectrode voltage-clamp and "slice" patch-clamp techniques. 2. Imi was associated with an increase of membrane conductance in 75% of DLSN neurons. There was no voltage-dependence of Imi between -60 and -140 mV; it exhibited a reversal potential of -17.0 +/- 5.3 mV (n = 14) determined by extrapolation of Imi and voltage relationship recorded using whole cell patch recording. Lowering extracellular sodium (26 mM) or potassium (1.4 mM) ions depressed Imi. 3. Imi was concentration dependent; 3 and 100 microM muscarine produced the minimum [22 +/- 4.6 pA, (mean +/- SE) n = 8] and maximum (167 +/- 28 pA, n = 7) responses, respectively. An EC50 was determined to be 15 microM (n = 8). Oxotremorine-methiodide (1-100 microM) also produced an inward current with similar potency compared with muscarine. On the other hand, McN-A-343 and pilocarpine (3-100 microM) did not produce any inward current in DLSN neurons. 4. Atropine (1 microM) completely reduced Im produced by 30 microM muscarine, whereas pirenzepine (PZP) shifted the concentration-response curve for muscarine in a parallel manner to the right. The EC50 for muscarine was shifted to 32, 52, and 204 microM by 0.2, 0.5, and 2 microM PZP, respectively. The apparent Kd value for PZP estimated by Schild plot analysis was 190 nM (n = 5). 5. Methoctramine (1 microM) also competitively depressed Imi; the calculated EC50 values were 26, 41, and 107 microM in concentrations of 0.2, 2, and 10 microM methoctramine, respectively. The apparent Kd for methoctramine was 420 nM. In contrast, AF-DX 116 (1 microM) did not significantly inhibit Imi. 6. Intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable analogue of GTP, suppressed irreversibly Imi. Pretreatment of DLSN neurons with pertussis toxin (PTX) did not prevent Imi (n = 8). 7. We suggest that muscarine causes this inward current by activating a M3 subtype of muscarinic receptor, which is coupled to a PTX-insensitive GTP-protein in rat DLSN neurons.
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PMID:Muscarine activates a nonselective cation current through a M3 muscarinic receptor subtype in rat dorsolateral septal nucleus neurons. 889 97

Alterations of autonomic tone can induce cardiac dysrhythmias. In the present experiments intravenous administration of epinephrine (15 micrograms/kg) caused dysrhythmias in rat hearts. Bilateral vagotomy or yohimbine treatment did not suppress the dysrhythmic effects of epinephrine. Atropine, glycopyrrolate, and pertussis toxin reduced the number of premature ventricular contractions and eliminated missed beats caused by epinephrine. Neostigmine increased the number of missed beats but did not change the number of premature ventricular contractions. These results indicate that epinephrine induces cardiac dysrhythmias in part by local release of acetylcholine. Muscarinic receptors and pertussis toxin sensitive G proteins are involved in epinephrine-induced arrhythmogenesis.
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PMID:Mechanism of epinephrine-induced dysrhythmias in rat involves local cholinergic activation. 896 56

1. Cytosolic Ca2+ concentration ([Ca2+]i) during exposure to acetylcholine or caffeine was measured in mouse duodenal myocytes loaded with fura-2. Acetylcholine evoked a transient increase in [Ca2+]i followed by a sustained rise which was rapidly terminated after drug removal. Although L-type Ca2+ currents participated in the global Ca2+ response induced by acetylcholine, the initial peak in [Ca2+]i was mainly due to release of Ca2+ from intracellular stores. 2. Atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, a muscarinic M3 antagonist), pirenzepine (a muscarinic M1 antagonist), methoctramine and gallamine (muscarinic M2 antagonists) inhibited the acetylcholine-induced Ca2+ release, with a high affinity for 4-DAMP and atropine and a low affinity for the other antagonists. Selective protection of muscarinic M2 receptors with methoctramine during 4-DAMP mustard alkylation of muscarinic M3 receptors provided no evidence for muscarinic M2 receptor-activated [Ca2+]i increase. 3. Acetylcholine-induced Ca2+ release was blocked by intracellular dialysis with a patch pipette containing either heparin or an anti-phosphatidylinositol antibody and by external application of U73122 (a phospholipase C inhibitor). 4. Acetylcholine-induced Ca2+ release was insensitive to external pretreatment with pertussis toxin, but concentration-dependently inhibited by intracellular dialysis with a patch pipette solution containing an anti-alpha q/alpha 11 antibody. An antisense oligonucleotide approach revealed that only the Gq protein was involved in acetylcholine-induced Ca2+ release. 5. Intracellular applications of either an anti-beta com antibody or a peptide corresponding to the G beta gamma binding domain of the beta-adrenoceptor kinase 1 had no effect on acetylcholine-induced Ca2+ release. 6. Our results show that, in mouse duodenal myocytes, acetylcholine-induced release of Ca2+ from intracellular stores is mediated through activation of muscarinic M3 receptors which couple with a Gq protein to activate a phosphatidylinositol-specific phospholipase C.
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PMID:Specific Gq protein involvement in muscarinic M3 receptor-induced phosphatidylinositol hydrolysis and Ca2+ release in mouse duodenal myocytes. 917 86

1. Acetylcholine causes a rise of intracellular Ca2+ in perisynaptic Schwann cells (PSCs) of the frog neuromuscular junction. The signalling pathway was characterized using the fluorescent Ca2+ indicator fluo-3 and fluorescence microscopy. 2. Nicotinic antagonists had no effect on Ca2+ responses evoked by ACh and no Ca2+ responses were evoked with the nicotinic agonist nicotine. The muscarinic agonists muscarine and oxotremorine-M induced Ca2+ signals in PSCs. 3. Ca2+ responses remained unchanged when extracellular Ca2+ was removed, indicating that they are due to the release of Ca2+ from internal stores. Incubation with pertussis toxin did not alter the Ca2+ signals induced by muscarine, but did block depression of transmitter release induced by adenosine and prevented Ca2+ responses in PSCs induced by adenosine. 4. The general muscarinic antagonists atropine, quinuclidinyl benzilate and N-methyl-scopolamine failed to block Ca2+ responses to muscarinic agonists. Atropine (at 20,000-fold excess concentration) also failed to reduce the proportion of cells responding to a threshold muscarine concentration sufficient to cause responses in less than 50% of cells. Only the allosteric, non-specific blocker, gallamine (1-10 microM) was effective in blocking muscarine-induced Ca2+ responses. 5. In preparations denervated 7 days prior to experiments, low concentrations of atropine reversibly and completely blocked Ca2+ responses to muscarine. 6. The lack of blockade by general muscarinic antagonists in innervated, in situ preparations suggests that muscarinic Ca2+ responses at PSCs are not mediated by any of the five known muscarinic receptors or that post-translational modification prevented antagonist binding.
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PMID:Muscarinic Ca2+ responses resistant to muscarinic antagonists at perisynaptic Schwann cells of the frog neuromuscular junction. 936 8

Effects of intrapancreatic cholinergic activation by electrical field stimulation (EFS) on secretin-stimulated pancreatic exocrine secretion were investigated in the totally isolated perfused rat pancreas. EFS at 15 V, 2 ms, and 8 Hz for 45 min markedly increased spontaneous pancreatic secretion. This increase was completely inhibited by tetrodotoxin (1 microM) but not by hexamethonium (100 microM). Atropine (2 microM) significantly reduced the EFS-evoked volume flow and amylase output by 52% and 80%, respectively. EFS further increased the secretin (12 pM)-stimulated pancreatic secretion of fluid and amylase. The increases of the two parameters were significantly suppressed by atropine by 28% and 72%, respectively. Interestingly, EFS significantly increased concentrations of somatostatin-like immunoreactivity in portal venous effluents. When pertussis toxin (200 ng/ml) or rabbit antisomatostatin serum (0.1 ml/10 ml; titer of 1:50,000) was intra-arterially administered, EFS further increased the secretin-stimulated pancreatic secretion. In conclusion, the activation of intrapancreatic cholinergic neurons potentiated the secretin action on pancreatic exocrine secretion in the rat. This potentiating effect was significantly reduced by local somatostatin released during EFS that activated intrapancreatic cholinergic tone.
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PMID:Significant cholinergic role in secretin-stimulated exocrine secretion in isolated rat pancreas. 948 97

Methoctramine, a selective M2 muscarinic cholinergic receptor antagonist, has been reported to activate phosphoinositide breakdown at high concentrations. Its polyamine structure suggests a putative activation of guanine nucleotide-binding proteins (G proteins). Incubation of methoctramine with rat peritoneal mast cells resulted in a dose-dependent noncytotoxic histamine release, with an EC50 of 20 microM and a maximum effect at 1 mM. Atropine, pirenzepine and HHSiD neither inhibited methoctramine-induced histamine release nor stimulated histamine release. Histamine release and inositol phosphates generation induced by methoctramine were both inhibited by pertussis toxin pretreatment. Benzalkonium chloride, a selective inhibitor of histamine secretion induced by basic secretagogues, inhibited the secretory response to methoctramine. [p-Glu5, D-Trp7,9,l0]-SPs5-11 (GPAnt-2), a well-characterized antagonist of G proteins, blocked the methoctramine-induced histamine release when the antagonist was allowed to reach its intracellular target by streptolysin O-permeabilization. The response to methoctramine was prevented by the hydrolysis of sialic acid residues of the cell surface by neuraminidase. The response of mast cells was restored by permeabilization of the plasma membrane. These results demonstrate that methoctramine, following its entry into the cell and the involvement of pertussis toxin-sensitive G proteins, activates phosphoinositide hydrolysis leading to mast cell exocytosis.
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PMID:The M2 muscarinic receptor antagonist methoctramine activates mast cells via pertussis toxin-sensitive G proteins. 960 19

Nitric oxide (NO) is a major transmitter in mediating cerebral neurogenic vasodilation in several species. Recent findings have suggested that acetylcholine, which is costored with NO in cerebral perivascular nerves, plays a role in modulating NO release, presumably by acting on muscarinic (M) receptors on nitric oxidergic nerve terminals. The present study was designed using an in vitro tissue bath technique to pharmacologically characterize the presynaptic muscarinic-receptor subtype(s) that mediate modulation of NO release and therefore neurogenic vasodilation and to investigate further the possible mechanisms involved in this presynaptic modulation in porcine basilar arteries. Transmural nerve stimulation (TNS) elicited a frequency-dependent, tetrodotoxin-sensitive relaxation. The relaxation was abolished by nitro-L-arginine (30 microM) and was completely reversed by L-arginine and L-citrulline, but not by their D-enantiomers. Atropine (0.01-1 microM), pirenzepine (an M1-receptor antagonist, 0. 01-1 microM), and methoctramine (an M2-receptor antagonist, 0.01-1 microM), but not 4-DAMP (an M3-receptor antagonist) or tropicamide (an M4-receptor antagonist) at concentrations as high as 10 mM, significantly increased the TNS-elicited relaxation. This relaxation, on the other hand, was significantly attenuated by arecaidine but-2-ynyl ester tosylate (an M2-receptor agonist, 0.1 microM) but was not affected by McN-A-343 (an M1-receptor agonist, 1 microM). Double-labeling immunohistochemical study demonstrated that perivascular M2 receptor-immunoreactive fibers were completely coincident with NADPH diaphorase fibers. Furthermore, the muscarinic receptor-mediated modulation of TNS-elicited relaxation was completely prevented by omega-conotoxin GVIA (0.1 microM), a specific N-type Ca2+ channel inhibitor, but was still observed in the presence of tetraethylammonium (1 mM), 8-bromo-cAMP (0.5 mM), and pertussis toxin. It is concluded that the presynaptic M2 receptors on porcine cerebral perivascular nitric oxidergic nerves mediate inhibition of NO release. The inhibition is due primarily to a decreased Ca2+ influx through N-type Ca2+ channels.
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PMID:Mechanism of prejunctional muscarinic receptor-mediated inhibition of neurogenic vasodilation in cerebral arteries. 988 33

The role of intrapancreatic neurons in the action of cholecystokinin (CCK) on pancreatic exocrine secretion of the totally isolated, perfused rat pancreas was investigated. Intrapancreatic neurons were activated by applying electrical field stimulation (EFS) to the isolated pancreas for 45 min. When applying EFS, spontaneous pancreatic secretions of fluid and amylase increased until the second 15-min period of EFS and then decreased during the third 15-min period. Atropine (2 microM) notably reduced the EFS-evoked pancreatic secretions of fluid and amylase. The CCK-induced (10 pM) pancreatic secretions of fluid and amylase elevated further in the first 15-min period of EFS and then gradually resumed to the levels observed during application of CCK alone in the third 15-min period of EFS. However, the CCK-induced pancreatic secretions remained elevated even in the third 15-min period of EFS when an action of endogenous somatostatin was inhibited by cyclo-(7-aminoheptanonyl-Phe-d-Trp-Lys-Thr[BZL]) (10 nM) or pertussis toxin (200 ng/ml). EFS further elevated spontaneous exocrine secretion by the cysteamine-treated (300 mg/kg) pancreas, but this was markedly reduced, to normal levels, by infusing somatostatin (100 pM). EFS increased the numbers of immunoreactive somatostatin cells in the Langerhans' islets. The results indicate that intrapancreatic neuronal activation influences CCK-induced pancreatic secretions in a dual-phase pattern in the rat: an increase during the early phase and a decrease during the late phase. Endogenous somatostatin released from the islets appears to inhibit the enhancing effect of neuronal activation on CCK-induced pancreatic secretion. Of the intrapancreatic neurons, the cholinergic ones appear to predominate in EFS's effects on CCK-induced pancreatic secretion.
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PMID:Effects of intrapancreatic neuronal activation on cholecystokinin-induced exocrine secretion of isolated perfused rat pancreas. 1008 62


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