Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle

Coburn, Ronald F.; Tomita, Tadao

doi:10.1152/ajplegacy.1973.224.5.1072

Cited by 239 publications

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“…central nervous system control of the airways; parasympathetic preganglionic neurons; choline acetyl transferase; vasoactive intestinal peptide; nitric oxide synthase; nucleus ambiguus; airway constriction; airway dilation IN MANY SPECIES, INCLUDING HUMANS, airway smooth muscle (ASM) tone critically relies on the balance between central excitatory cholinergic control (3,19,33,49) and the inhibitory nonadrenergic, noncholinergic (iNANC) influences (2,12,17,47,56). Activation of cholinergic preganglionic neurons produces airway constriction, submucosal gland secretion and increased blood flow using acetylcholine as a neurotransmitter (23,25,26).…”

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“…Activation of cholinergic preganglionic neurons produces airway constriction, submucosal gland secretion and increased blood flow using acetylcholine as a neurotransmitter (23,25,26). In the presence of cholinergic and sympathetic blockade, stimulation of vagal nerves, either by electrical current or via neural reflex pathways, elicits relaxation of preconstricted ASM cells via activation of iNANC pathways (2,12,17,56). Recent studies indicate that the iNANC system employs vasoactive intestinal peptide (VIP) (7,16,22,38,47,57), nitric oxide (NO) (4,30,36,44,51), or both (6, 14 -16, 64) to elicit ASM relaxation.…”

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Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Mayer

Haxhiu

2004

Journal of Applied Physiology

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Kc, Prabha, Catherine A. Mayer, and Musa A. Haxhiu. Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons. J Appl Physiol 97: 1508 -1517, 2004; 10.1152/japplphysiol.00282.2004.-In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin ␤-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) cholinergic neurons innervating the airways coexpress ChAT and VIP but do not contain NOS, and 3) chemical stimulation of the rostral nucleus ambiguus had no significant effect on precontracted airway smooth muscle tone after muscarinic receptor blockade. These studies indicate that vagal preganglionic neurons are cholinergic in nature and coexpress VIP but do not contain NOS; their stimulation increases cholinergic outflow, without activation of inhibitory nonadrenergic, noncholinergic ganglionic neurons, stimulation of which induces airway smooth muscle relaxation. Furthermore, these studies do not support the possibility of direct inhibitory innervation of airway smooth muscle by vagal preganglionic fibers that contain VIP.central nervous system control of the airways; parasympathetic preganglionic neurons; choline acetyl transferase; vasoactive intestinal peptide; nitric oxide synthase; nucleus ambiguus; airway constriction; airway dilation IN MANY SPECIES, INCLUDING HUMANS, airway smooth muscle (ASM) tone critically relies on the balance between central excitatory cholinergic control (3,19,33,49) and the inhibitory nonadrenergic, noncholinergic (iNANC) influences (2,12,17,47,56). Activation of cholinergic preganglionic neurons produces airway constriction, submucosal gland secretion and increased blood flow using acetylcholine as a neurotransmitter (23,25,26). In the presence of cholinergic and sympathetic blockade, stimulation of vagal nerves, either by electrical current or via neural reflex pathways, elicits relaxation of preconstricted ASM cells via activation of iNANC pathways (2,12,17,56). Recent studies indicate that the iNANC system employs vasoactive intestinal peptide (VIP) (7,16,22,38,47,57), nitric oxide (NO) (4, 30, 36, 44, 51), or both (6, 14 -16, 64) to elicit ASM relaxation. Ho...

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confidence: 99%

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confidence: 99%

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Mayer

Haxhiu

2004

Journal of Applied Physiology

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“…None of these relaxations was affected by propranolol or ouabain. All ofthe K+-induced relaxations were partially or completely in- (Hay & Wadsworth, 1984;Bryson et al, 1985 (Kirkpatrick, 1975;Foster et al, 1983b , 1964) has been suggested for the guinean is part of the response of the pig trachealis (Coburn & Tomita, 1973 …”

Section: Resultsmentioning

confidence: 93%

Tetrodotoxin‐sensitive, K⁺‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca²⁺‐entry blocking drugs, Ca²⁺‐free solution and after polyamine exposure

Chideckel

Fedan

Mike

1986

British J Pharmacology

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1 We have previously observed a paradoxical relaxant effect of K+ on guinea-pig isolated trachealis after exposure to polyamines. The purpose of the present study was to evaluate whether the relaxation involved a reduction in the entry ofextracellular Ca2+. We therefore investigated the effect of K+ in the presence of Ca2+-entry blocking drugs and in the presence of Ca2+-free solution. 3 A relaxation in response to K+ was also observed in Ca2+-free solution, (with tone induced by methacholine), an effect not blocked by propranolol or ouabain. 4 Tetraethylammonium (30mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol. 5 Tetrodotoxin (10-6 M) (TTX) blocked 65% of the K+-induced relaxation in the presence of nifedipine and 100% of K+-induced relaxation either in a Ca2+-free solution or after polyamine exposure. TTX was without effect on TEA-induced relaxation after Ca2+-entry blocking drugs.6 Atropine (10-6 M) or hexamethonium (10-6 M) did not affect K+-induced relaxation after polyamine exposure. 7 The concentration-response curve for K+-induced contraction in normal modified Krebs-Henseleit solution was shifted to the left by TTX. 8 It is concluded: (a) K+ has a direct effect on the trachealis causing contraction and an indirect effect, mediated by neurotransmitter release, causing relaxation. This latter effect is exposed when the direct effect is inhibited by Ca2+-entry blocking drugs, Ca2+-free solution or polyamine exposure; the indirect effect is non-adrenergic, non-cholinergic and not via ganglionic transmission; (b) the TEAinduced relaxation and a component of the K+ -induced relaxation after Ca2+ blocking drugs cannot be explained by neurotransmitter release; (c) polyamines may act as naturally occurring Ca2+ antagonists.

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“…The mechanism controlling the direction of the NANC response is probably postganglionic, since we used electrical field stimulation which is thought to activate nerves postganglionically (Coburn & Tomita, 1973;Skoogh, 1986). Based on the present data, however, it is not possible to differentiate between a pre-and a postjunctional site for this mechanism but this mechanism does appear to be independent of the cyclo-oxygenase system, since indomethacin was continuously present in our study.…”

Section: Reproducibility Of Nanc Responsesmentioning

confidence: 99%

Non‐adrenergic, non‐cholinergic neural activation in guinea‐pig bronchi: powerful and frequency‐dependent stabilizing effect on tone

Lindén¹,

Ullman

Skoogh³

1993

British J Pharmacology

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1 We examined non-adrenergic, non-cholinergic (NANC) stimulation for its stabilizing effect on bronchial smooth-muscle tone with respect to its regulatory power and the effect of variations in neural impulse frequency.2 The guinea-pig isolated main bronchus (n = 4-12) 4 There was a difference of approximately 90% of maximum between the highest and the lowest tone level prior to NANC activation. This difference was reduced by the converging contractile and relaxant NANC responses and the magnitude of this 'convergence effect' was 40(8)% at 1 Hz, 72(4)% at 3 Hz and 90(2)% at 10 Hz. 5 These findings indicate that NANC neural activation stabilizes bronchial smooth-muscle tone via a contraction when the tone is low prior to activation and via a relaxation when the tone is high prior to activation. The NANC stabilizing effect on tone appears to be powerful and its magnitude can be controlled by the neural impulse frequency. The level of tone towards which the NANC responses converge does not appear to be markedly altered by variations in the impulse frequency. Our findings are consistent with a regulatory role for NANC responses in the control of bronchial smooth-muscle tone.

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Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle

Cited by 239 publications

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Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Tetrodotoxin‐sensitive, K⁺‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca²⁺‐entry blocking drugs, Ca²⁺‐free solution and after polyamine exposure

Non‐adrenergic, non‐cholinergic neural activation in guinea‐pig bronchi: powerful and frequency‐dependent stabilizing effect on tone

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Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle

Cited by 239 publications

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Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Tetrodotoxin‐sensitive, K+‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca2+‐entry blocking drugs, Ca2+‐free solution and after polyamine exposure

Non‐adrenergic, non‐cholinergic neural activation in guinea‐pig bronchi: powerful and frequency‐dependent stabilizing effect on tone

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Tetrodotoxin‐sensitive, K⁺‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca²⁺‐entry blocking drugs, Ca²⁺‐free solution and after polyamine exposure