The role of nitric oxide in cholinergic neurotransmission in rat trachea

Sekizawa, Kiyohisa; Fukushima, Toshiro; Ikarashi, Yasushi; Maruyama, Yūji; Sasaki, Hidetada

doi:10.1111/j.1476-5381.1993.tb13885.x

Cited by 40 publications

(27 citation statements)

References 23 publications

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“…These results were consistent with that of Seki zawa et al (4) who demonstrated that L-NMMA increas ed EFS-induced ACh release from the rat trachea and also with that of Jing et al (5) who demonstrated that another NO synthase inhibitor, Nc-nitro-L-arginine (L-NNA), increased EFS-induced excitatory junctional potential which is an index of cholinergic neurotransmission.…”

Section: Discussionsupporting

confidence: 82%

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Abnormal Modulation of Cholinergic Neurotransmission by Endogenous Nitric Oxide in the Bronchus of Rats with Hyperresponsiveness Induced by Allergen Challenge.

Misawa

Sato

1997

Jpn.J.Pharmacol

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ABSTRACT-The involvement of endogenous nitric oxide (NO) in bronchial cholinergic neurotransmission was compared between normal rats and airway hyperresponsive (AHR) rats. Male Wistar rats were sensi tized and repeatedly challenged with dinitrophenylated (DNP)-Ascaris antigen. Twenty-four hours after the last antigenic challenge, enhancements of both the electrical field stimulation (EFS)-induced bronchocon striction and acetylcholine (ACh) release were observed. NG-Monomethyl-L-arginine (L-NMMA; NO syn thase inhibitor, 0.1 mM) augmented the EFS-induced bronchoconstriction and ACh release without affect ing exogenously applied ACh-induced bronchoconstriction in normal rats. Interestingly, the augmentative effects of L-NMMA seen in normal rats were not manifested in AHR rats. Sodium nitroprusside inhibited the EFS-induced bronchoconstriction in a concentration-dependent manner; the inhibition was much larger than that of exogenously applied ACh-induced constriction in both normal and AHR rats. Furthermore, dibutyryl cGMP (3 mM) inhibited the EFS-induced bronchoconstriction with no effect on the ACh-induced bronchoconstriction in both normal and AHR rats. These findings suggest that endogenous NO may have a modulatory role in bronchial cholinergic neurotransmission in normal rats and that the augmented ACh release in the AHR rats may result from the defect of endogenous NO-induced modulation of cholinergic nerve transmission.Keywords: Airway hyperresponsiveness, Nitric oxide, Cholinergic neurotransmission, Nitrergic dysfunction, Dinitrophenylated (DNP)-AscarisNitric oxide (NO) may play an important regulatory role in airway functions as an inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitter in many spe cies including humans (1-3). It has been demonstrated that neurally released NO not only relaxes tracheal smooth muscle but also inhibits acetylcholine (ACh) re lease from tracheal cholinergic nerves in rats and cats (4, 5). Furthermore, excessively produced NO from macro phages, leuckocytes and epithelium of airways may take part in airway diseases (6).Increased ACh release from cholinergic nerves may be an important mechanism that contributes to airway hyperresponsiveness in bronchial asthma (7). The ACh overrelease might be related to dysfunction of the modulatory NO pathway in cholinergic neurotransmis sion; however, the role of endogenous NO in accelerated cholinergic neurotransmission in airway hyperresponsive ness has not been confirmed.The purpose of the present study was to determine whether NO has a modulatory effect on bronchial cholinergic neurotransmission in normal rats and whether any alteration of the modulatory effect of NO takes place in airway hyperresponsiveness. We therefore investigated the effects of an NO synthase (NOS) inhibitor, NG monomethyl-L-arginine (L-NMMA), on both the choliner gic bronchoconstriction and amount of released ACh from bronchial tissue evoked by electrical field stimula tion (EFS) in normal rats and dinitrophenylated (DNP) Ascaris antigen-induced airway hyp...

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Section: Discussionsupporting

confidence: 82%

“…It has been demonstrated that neurally released NO not only relaxes tracheal smooth muscle but also inhibits acetylcholine (ACh) re lease from tracheal cholinergic nerves in rats and cats (4,5). Furthermore, excessively produced NO from macro phages, leuckocytes and epithelium of airways may take part in airway diseases (6).…”

mentioning

confidence: 99%

Abnormal Modulation of Cholinergic Neurotransmission by Endogenous Nitric Oxide in the Bronchus of Rats with Hyperresponsiveness Induced by Allergen Challenge.

Misawa

Sato

1997

Jpn.J.Pharmacol

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“…Upon concomitant release, NO and acetylcholine functionally antagonize each other. It has also been shown that NO is able to modulate cholinergic responses by prejunctional inhibition of acetylcholine release in the guinea-pig ileum (Wiklund et al, 1993;Kilbinger & Wolf, 1994;Hebeiû & Kilbinger, 1996), canine ileum (Hryhorenko et al, 1994) and rat trachea (Sekizawa et al, 1993). Two lines of results in the pig gastric fundus suggest that the potentiating e ect of L-NAME on the electrically induced contractions re¯ects only functional antagonism of acetylcholine by NO.…”

Section: Discussionmentioning

confidence: 55%

Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus

Leclere¹,

Lefebvre²

1998

British J Pharmacology

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1 The interaction between the cholinergic and nitrergic innervation was investigated in circular muscle strips of the pig gastric fundus. 2 In physiological salt solution containing 4610 76 M guanethidine, electrical ®eld stimulation (EFS; 40 V, 0.5 ms, 0.5 ± 32 Hz, 10 s at 4 min intervals) induced small transient relaxations at 0.5 ± 4 Hz, and large frequency-dependent contractions, sometimes followed by o -relaxations, at 8 ± 32 Hz. 3 In the presence of L-N G -nitroarginine methyl ester (L-NAME; 3610 74 M) or physostigmine (10 76 M), relaxations were reversed into contractions and contractions were enhanced. Physostigmine added to L-NAME further enhanced contractions, while addition of L-NAME to physostigmine had no additional e ect. O -relaxations were enhanced in the presence of L-NAME and physostigmine. L-NAME and physostigmine consistently increased basal tone. 4 Tissues contracted by 5-hydroxytryptamine or by acetylcholine responded to EFS in a similar way as in basal conditions and L-NAME reversed the relaxations at the lower stimulation frequencies into contractions and enhanced the contractions at the higher stimulation frequencies. 5 O -relaxations in the presence of L-NAME were partially reduced by a-chymotrypsin (10 U ml 71 ). 6 In the absence of physostigmine, the concentration-response curve to exogenous acetylcholine was not in¯uenced by L-NAME. 7 Contractions of the same amplitude induced by EFS at 4 Hz and by exogenous acetylcholine were either decreased or enhanced to the same extent by sodium nitroprusside (SNP; 10 75 M), depending upon the degree of relaxation by SNP. 8 These experiments suggest that endogenous nitric oxide interferes with cholinergic neurotransmission in the pig gastric fundus by functional antagonism at the postjunctional level. The interaction is independent of the degree of contraction.

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“…However, it was reported that inhibition of NO synthesis had no effect on acetylcholine (ACh) release in the human and guinea-pig airway [23,24]. However, in contrast, SEKIZAWA et al [25] had shown that NO synthesis inhibitor, N G -monomethyl-L-arginine (L-NMMA), significantly enhances the ACh release from the vagus nerve terminal evoked by EFS in the guineapig trachea. Thus, it seems plausible to postulate that NO, when released from nerve terminals, may directly relax airway muscle through pharmacomechanical coupling, and at the same time inhibit the release of ACh from the vagus nerve terminal, thus playing a "double braking" role in bronchoconstriction [6,7,26].…”

Section: Discussionmentioning

confidence: 98%

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

Aizawa

Tanaka²,

Sakai³

et al. 1997

Eur Respir J

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The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N ω -nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat.To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10 -5 M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin.These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation. Eur Respir J 1997; 10: 314- Neurally-mediated relaxation of airway smooth muscle in various animal species, including man, is largely nonadrenergic and noncholinergic (NANC) (see, for example, [1]). Although the neurotransmitter(s) responsible for NANC relaxation in the airways have not been conclusively identified, nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) have emerged as strong candidates [2][3][4][5][6][7].In cat airway, we have shown that NANC relaxation can be classified into two components by thresholds for activation or by sensitivity to N ω -nitro-L-arginine methylester (L-NAME), and that the pattern of L-NAME-sensitive and -insensitive components differs in central and peripheral airways [6,7]. Specifically, electrical field stimulation (EFS) elicited monophasic relaxation in the trachea, confirming previous observations [5,8], but biphasic NANC relaxations, comprising an initial fast component followed by a second slow component in the bronchioles. L-NAME selectively abolished the first component of NANC relaxation without affecting the second in bronchioles, whilst, in the trachea, L-NAME completely suppressed the monophasic NANC relaxation after single or short repetitions (<5) of 1 ms pulse stimuli; however, after more stimuli (>10) of 1 or 4 ms duration, suppression of NANC relaxation was incomplete (to 40-50% of the control value) [7]. VIP antagonists partially suppressed the L-NAME-resistant NANC relaxation....

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The role of nitric oxide in cholinergic neurotransmission in rat trachea

Cited by 40 publications

References 23 publications

Abnormal Modulation of Cholinergic Neurotransmission by Endogenous Nitric Oxide in the Bronchus of Rats with Hyperresponsiveness Induced by Allergen Challenge.

Abnormal Modulation of Cholinergic Neurotransmission by Endogenous Nitric Oxide in the Bronchus of Rats with Hyperresponsiveness Induced by Allergen Challenge.

Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

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