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)

To examine the role of leukotriene D4 (LTD4) in early and late pulmonary responses to antigen, we evaluated the effects of two LTD4, antagonists, MK-571 and FPL-57231, on the changes in pulmonary resistance (RL) in the 8-h period following antigen challenge of allergic rats. A total of 69 rats, aged 6 to 8 wk, were sensitized to subcutaneous ovalbumin (OA, 1 mg) and intraperitoneal Bordetella pertussis vaccine (6 x 10(9) bacilli). At 14 days after sensitization, rats were anesthetized with intraperitoneal urethane (1.1 g/kg) and intubated endotracheally. Aerosols of OA (5% wt/vol in saline for 5 min) were administered to 24 control rats, to 11 rats that were pretreated with aerosolized FPL-57231, and to 8 rats that were pretreated with MK-571; 6 rats also received MK-571 at 2 h after OA. A control group of 13 rats was challenged with aerosols of saline. We defined an early response (ER) as an increase in RL to at least 150% of the postsaline value occurring within 1 h after OA challenge. A late response (LR) was defined as a value of RL exceeding the mean plus 2 SD of all values of RL from 75 min to 8 h after OA challenge and lasting at least 30 min. An ER was observed in 17 of 24 control rats, in 8 of 11 FPL-57231-pretreated rats, and in 3 of 8 MK-571-pretreated rats (not significant). The magnitude and duration of the ER were significantly reduced by MK-571, whereas only the duration was affected by FPL-57231.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of leukotriene D4 in the early and late pulmonary responses of rats to allergen challenge. 238 99

The sensitization of guinea pigs with ovalbumin and Bacillus pertussis vaccine caused an increase (P less than 0.001) in the resting membrane potential (Em) of airway smooth muscle (ASM) cells, from -61.3 +/- 0.5 mV (+/- SE) to -72.7 +/- 0.6 mV (+/- SE). One, two, and three weeks after resensitization of sensitized animals with ovalbumin, Em further increased (P less than 0.001) to -76.2 +/- 0.2 mV (+/- SE), -77.4 +/- 0.3 mV, and -78.1 +/- 0.5 mV, respectively. Similarly, both in vivo and in vitro passive sensitization caused an increase (P less than 0.001) in Em of ASM cells to -69.5 +/- 0.3 mV and -68.5 +/- 0.4 mV, respectively. ASM preparations isolated from rabbits showed a similar increase (P less than 0.001) in Em after passive in vitro sensitization with serum from ovalbumin-sensitized rabbits. An increase in the contribution of the electrogenic Na+-pump was found to be responsible for the observed changes in Em following both active and passive sensitization. The presence of diphenhydramine (anti-H1), methysergide, indomethacin, 5,8,11,14-eicosatetraenoic acid (ETYA), FPL 55712 (a leukotriene receptor blocker), phenoxybenzamine, and disodium cromoglycate (a stabilizing agent) during passive in vitro sensitization failed to prevent an increase in the Em of ASM cells. However, incubation of normal guinea pig and rabbit ASM preparations with heated serum (60 degrees C for 2 hours) from ovalbumin-sensitized guinea pigs or rabbits partially inhibited (in guinea pigs) or completely abolished (in rabbits) such an increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations of airway smooth muscle cell membrane by sensitization. 241 8

Rats were sensitized with a single intraperitoneal dose of bovine serum albumin in alhydrogel plus Bordetella pertussis vaccine, and local anaphylaxis was elicited in the paw by soluble antigen 2 weeks later. The response was mainly due to IgE-type antibodies and proved to be highly sensitive to beta-adrenoceptor agonists. Dexamethasone inhibited the response after a lag phase. Methysergide, disodium chromoglycate, diethylcarbamazine, BW 775/c, nordihydroguarjaretic acid, and FPL 55712 were also suppressive, while mepyramine was without effect. A synergism between methysergide and FPL 55712 was shown. Active local paw anaphylaxis appears to be adequate and easily applicable for large-scale screening of anti-allergic drugs.
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PMID:A new method of testing anti-allergic drugs. 634 Dec 56

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.
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PMID:Muscarinic receptor activation modulates Ca2+ channels in rat intracardiac neurons via a PTX- and voltage-sensitive pathway. 931 Apr 37

1. Muscarinic agonist specificity is limited, making it difficult to match receptor subtypes with signal transduction cascades that mediate ion channel modulation. We have characterized the inhibitory effects of two muscarinic agonists, oxotremorine-M (Oxo-M) and bethanechol chloride (BeCh), on Ca(2+) currents in neonatal rat superior cervical ganglion neurons. 2. Oxo-M-mediated (10 micro M) inhibition occurred via two signaling pathways. The first pathway inhibited whole cell peak currents, consisting primarily of N-type current, but not FPL 64176-induced, long-lasting tail currents, comprised entirely of L-type current. Inhibited currents displayed slowed activation kinetics and voltage dependence, characteristics of membrane-delimited inhibition. Current inhibition was blocked by the selective M(2) receptor antagonist, methoctramine (METH; 100 nM), or following pertussis toxin (PTX) pretreatment. 3. Activation of the second pathway inhibited both peak and long-lasting tail currents. This pathway was voltage-independent, PTX-insensitive, but sensitive to internal Ca(2+) chelator concentration. Muscarinic toxin 7 (MT-7, 100 nM), an irreversible M(1) receptor antagonist, eliminated this inhibition. Oxo-M (100 micro M) decreased L- and N-type channel activities in cell-attached patches, indicating that a diffusible second messenger is involved. 4. BeCh (100 micro M) also inhibited whole cell currents via the membrane-delimited pathway. Blocking M(4) receptors with 100 nM pirenzepine (in the presence of MT-7) had no effect, while antagonizing M(2) receptors with METH abolished inhibition. Concentrations of BeCh as high as 3 mM failed to inhibit either peak or long-lasting tail currents following PTX pretreatment. 5. These results indicate that BeCh may be an effective tool for selectively activating M(2) receptor stimulation of the membrane-delimited pathway.
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PMID:Pharmacological discrimination between muscarinic receptor signal transduction cascades with bethanechol chloride. 1271 15