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S Itabashi

Publications and source records attributed to S Itabashi.

13 recordsLinked to original sources

Evidence that an atypical beta-adrenoceptor mediates the prejunctional inhibition of non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We investigated the effect of the putative beta 3 agonist BRL 35135 on non-adrenergic non-cholinergic (NANC) contractions in guinea-pig bronchial strips. BRL 35135 (10(-9) to 10(-6) M) did not alter the baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion without having a significant effect on the contraction induced by substance P (10(-6) M). BRL 35135 (10(-6) M) also reduced the contraction induced by capsaicin (10(-7) M). Likewise, BRL 37344 (10(-9) to 10(-6) M) reduced NANC contractions induced by EFS in a concentration-dependent fashion. While BRL 37344 up to concentrations of 10(-8) M did not alter the contraction induced by SP (10(-6) M), BRL 37344 (10(-8) M) significantly inhibited NANC contractions induced by EFS and capsaicin (10(-7) M), (P less than 0.01). The inhibitory effect of BRL 35135 (10(-6) M) on NANC contractions induced by EFS was not significantly altered by the non-selective beta-adrenoceptor antagonists, propranolol and pindolol (P greater than 0.10), by the beta 1-selective antagonists, atenolol and metoprolol (P greater than 0.20) (10(-8) to 10(-6) M), or by the alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5) M) (P greater than 0.50). These results suggest that beta 3 agonists exert a prejunctional inhibitory action on NANC contractions.

Animals

The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However, forskolin (less than 1 microM) did not alter the contraction induced by substance P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP (1 microM)-induced contractions. 5. In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 microM). 6. These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.

Animals

gamma-Aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells.

1. The pharmacologic properties of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in the paratracheal ganglion cells freshly dissociated from 7- to 10-day-old rat trachea in a whole-cell recording mode by the use of a conventional patch-clamp technique. 2. GABA- and muscimol-induced currents increased sigmoidally in a concentration-dependent manner, and both currents reversed at approximately -3 mV, which was close to the Cl- equilibrium potential (ECl). 3. Strychnine (STR) at low concentration and bicuculline (BIC) inhibited GABA response competitively, whereas STR at the higher concentrations, benzylpenicillin (PCG), or picrotoxin (PTX) inhibited noncompetitively. Inhibition of GABA response by PCG but not other antagonists was voltage dependent, indicating that PCG acts as a Cl- channel blocker. 4. The concentration-response curve of pentobarbital sodium (PB)-induced ICl was bell shaped. At concentrations higher than 10(-3) M, both the peak and plateau currents decreased, and a transient "hump" current appeared immediately after washing out PB. In the presence of PB, the concentration-response curve of GABA shifted toward left without changing the maximum response. 5. Although diazepam (DZP) at concentration used did not induce a response, it potentiated the GABA response in a concentration-dependent manner between 10(-8) and 10(-6) M. DZP also caused a parallel shift toward left in the concentration-response curve of GABA. 6. PB or DZP further enhanced the GABA response in the presence of the other agent. 7. It is concluded that the properties of GABAA receptors in the paratracheal ganglion cells are essentially similar to those reported in other preparations.

Animals

Pre- and postjunctional muscarinic receptor subtypes in dog airways.

To examine muscarinic receptor subtypes involved in cholinergically mediated contractions of the airway, we studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, AF-DX 116, the M3-selective antagonist, 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP) methiodide, and the non-selective antagonist, atropine, on acetylcholine (ACh)- and electrically induced contractions in dog bronchi and bronchioles. The relative potencies of the antagonists based on IC50 values of each antagonist for contractions induced by the two concentrations of ACh that produced 50% of the maximum (ED50) and the maximum (EDmax) contractions and the pA2 values were atropine greater than or equal to 4-DAMP methiodide greater than pirenzepine = AF-DX 116 in both the bronchi and bronchioles. The IC50 and pA2 values of each antagonist did not differ significantly between the bronchi and bronchioles. 4-DAMP methiodide significantly inhibited the contractile response to electrical field stimulation (EFS) at 5 Hz at concentrations that did not alter the contractile responses to exogenous ACh in both the bronchi and bronchioles, whereas pirenzepine, AF-DX 116 and atropine inhibited the EFS-induced contraction only at the concentrations that reduced the contraction induced by exogenous ACh. The present results suggest that the cholinergic contraction is mediated via the postsynaptic receptor M3, based on functional potencies of muscarinic antagonists and presynaptic receptor auto-facilitatory M3, based on the suppression of the contractile response to EFS by 4-DAMP methiodide in central and peripheral airways.

Acetylcholine

Inhibitory actions of prostaglandin E1 on non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We have investigated the effect of prostaglandin E1 (PGE1) on non-adrenergic, non-cholinergic (NANC) contraction in guinea-pig bronchial strips. PGE1 (10 nM to 10 microM) did not alter baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 6.60 +/- 0.10 M and maximum inhibition was 88.7 +/- 2.9%). PGE1 (greater than 0.3 microM) also reduced the contraction induced by substance P (1 microM). Removal of epithelium did not alter the effects of PGE1 on NANC contraction. These results suggest that PGE1 exerts both pre- and post-junctional inhibitory actions on NANC contraction.

Alprostadil

Nonadrenergic inhibitory nerves attenuate neurally mediated contraction in cat bronchi.

Effects of nonadrenergic and noncholinergic (NANC) inhibitory nerves on cholinergic neurotransmission were examined in isolated bronchial segments from cats in the presence of propranolol (10(-6) M) and indomethacin (10(-6) M) by use of electrical field stimulation (EFS) techniques. EFS caused contraction alone in tissues at the baseline tension and biphasic responses (contraction and relaxation) in tissues precontracted with 5-hydroxytryptamine. Contraction was abolished by atropine (10(-6) M), and relaxation was abolished by tetrodotoxin (10(-6) M). At the baseline tension, EFS at frequencies greater than 10 Hz inhibited the subsequent (4 min later) contraction induced by EFS at 1-5 Hz. EFS-induced inhibition was stimulus frequency dependent and reached maximum at 20 Hz. However, EFS at 20 Hz did not inhibit the subsequent contractile response to acetylcholine (10(-7) to 10(-3) M). Exogenously applied vasoactive intestinal peptide mimicked EFS-induced inhibitory effects, but substance P and calcitonin gene-related peptide did not. The inhibitory effect of EFS at 20 Hz was not altered by pyrilamine, cimetidine, naloxone, methysergide, phentolamine, BW755C, AF-DX 116, or removal of epithelium. These results imply that the NANC transmitter acts via presynaptic cholinergic receptors.

Animals

Allergic sensitization in elderly patients with chronic obstructive pulmonary disease.

To study whether allergic sensitization occurs in elderly patients with chronic pulmonary obstructive disease (COPD), we examined serum IgE and skin test reactivity to allergens in three age-matched groups of normal subjects, and in patients with COPD and bronchial asthma (BA). Serum IgE was significantly higher in patients with COPD and BA than in normal subjects (p less than 0.05), and patients with COPD showed serum IgE levels as high as those of patients with BA. However, the skin test scores were significantly higher in patients with BA than in normal subjects and patients with COPD (p less than 0.05). Neither serum IgE nor skin test score significantly correlated with FEV1%, PaO2, PaCO2 or Brinkman's Index in any group (p greater than 0.20). These results suggest that allergic sensitization occurs in elderly patients with COPD and that symptoms associated with COPD may be partly due to allergic inflammation.

Asthma

Eosinophil supernatant causes hyperresponsiveness of airway smooth muscle in guinea pig trachea.

To study the role of eosinophils in airway hyperresponsiveness, we studied the effect of supernatant obtained from activated eosinophils on the responses of isolated guinea pig tracheal smooth muscle segments to histamine. Eosinophils obtained from guinea pig peritoneal fluid were purified and activated with Ca2+ ionophore A23187 using a two-stage reaction. Supernatant obtained from different eosinophil cell numbers (3 x 10(5) to 10(7) cells) did not alter resting tension but potentiated the contractile response to histamine in a cell number-dependent fashion. Thus, at a cell number of 10(7), the supernatant decreased the mean (+/- SE) log histamine concentration producing 50% of maximum contraction significantly from a control value of -5.62 +/- 0.10 to -5.99 +/- 0.07 M (p less than 0.05). The potentiating effect of the supernatant (10(7) cells) was not altered by either removal of tracheal epithelium or by pretreatment with indomethacin when cells were activated. However, pretreatment with AA 861 completely inhibited the supernatant (10(7) cells)-induced potentiating effect associated with inhibition of leukotriene C4, D4, and E4 release in the supernatant. The concentrations of exogenous authentic leukotrienes chosen to match concentrations in the supernatant mimicked the supernatant-induced potentiating response to histamine. These results suggest that leukotrienes released from eosinophils cause hyperresponsiveness of airway smooth muscle in vitro.

Animals

Permanent brain damage possibly caused by theophylline in two elderly patients with airway obstruction.

Two aged patients with bronchial asthma and chronic obstructive pulmonary disease who suffered convulsions that resulted in permanent brain damage during treatment with the recommended therapeutic dose of theophylline are presented here. A dose or concentration of theophylline lower than the recommended one should be considered in the treatment of some aged patients with pulmonary obstructive disease.

Aged

Prolonged hypoxemia after 10 min walking exercise in aged patients with chronic obstructive pulmonary disease.

Although the behavior and factors of exercise tolerance have been studied during exercise in patients with chronic obstructive pulmonary disease (COPD), little attention has been paid to the after-effects of such activity. Arterial oxygen saturation (SaO2) was monitored during and after a 10 min walking exercise in aged patients with COPD. Neither baseline SaO2 nor mean SaO2 during exercise correlated to the 10 min walking distance. However, the recovery time of SaO2 to the baseline value shows significant correlation to the 10 min walking distance. Careful attention should be paid to prolonged hypoxemia after exercise in severe cases of COPD.

Aged