Nonadrenergic inhibitory nervous system in human airways

1976 ◽  
Vol 41 (5) ◽  
pp. 764-771 ◽  
Author(s):  
J. Richardson ◽  
J. Beland
Keyword(s):  
Smooth Muscle ◽  
Gastrointestinal Tract ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Inhibitory System ◽  
Electrical Field ◽  
Human Airways ◽  
Adrenergic Blocking ◽  
Stimulation Of

Human airways, from the middle of the trachea to the distal bronchi, were studied in vitro for the presence of inhibitory nerves. The tissue was obtained from operations and from recent autopsies. Electrical field stimulation of the tissues demonstrated cholinergic, excitatory nerves and their effect was blocked by atropine. Field stimulation of the tissues, in the presence of atropine, relaxed the smooth muscle even when the muscle was contracted by histamine. The field stimulation-induced relaxation was neither blocked nor modified by adrenergic blocking agents. Maximum relaxation of the bronchial muscle was obtained with a pulse duration of 1–2 ms, 70 V,and frequencies of 20 Hz and greater. The tracheal smooth muscle showed 85%of maximal relaxation with a frequency of 10 Hz. Tetrodotoxin, blocked the field stimulation-induced relaxation for pulse durations of 2 ms; this indicated that nerves were being stimulated. The airway system shows some of the characteristics of the nonadrenergic inhibitory system in the gastrointestinal tract and of the system reported in the guinea pig trachealis muscle.No evidence of adrenergic inhibitory fibers was found in the bronchial muscle with either pharmacological or histochemical techniques. These findings suggest that the nonadrenergic inhibitory system is the principal inhibitory system for the smooth muscle of human airways. We suggest that a defect in the airway system, such as that shown in the gastrointestinal tract, may be an explanation for the hyperreactive airways of asthma and chronic bronchitis.

Release of epithelium-derived PGE2 from canine trachea after antigen inhalation

1998 ◽  
Vol 274 (2) ◽  
pp. L220-L225 ◽  
Author(s):  
I. McGrogan ◽  
L. J. Janssen ◽  
J. Wattie ◽  
P. M. O’Byrne ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Organ Bath ◽  
Field Stimulation ◽  
Electrical Field ◽  
Concentration Response Curve

To investigate the role of prostaglandin (PG) E2 in allergen-induced hyperresponsiveness, dogs inhaled either the allergen Ascaris suum or vehicle (Sham). Twenty-four hours after inhalation, some animals exposed to allergen demonstrated an increased responsiveness to acetylcholine challenge in vivo (Hyp-Resp), whereas others did not (Non-Resp). Strips of tracheal smooth muscle, either epithelium intact or epithelium denuded, were suspended on stimulating electrodes, and a concentration-response curve to carbachol (10−9 to 10−5 M) was generated. Tissues received electrical field stimulation, and organ bath fluid was collected to determine PGE2content. With the epithelium present, all three groups contracted similarly to 10−5 M carbachol, whereas epithelium-denuded tissues from animals that inhaled allergen contracted more than tissues from Sham dogs. In response to electrical field stimulation, Hyp-Resp tissues contracted less than Sham tissues in the presence of epithelium and more than Sham tissues in the absence of epithelium. PGE2release in the muscle bath was greater in Non-Resp tissues than in Sham or Hyp-Resp tissues when the epithelium was present. Removal of the epithelium greatly inhibited PGE2release. We conclude that tracheal smooth muscle is hyperresponsive in vitro after in vivo allergen exposure only when the modulatory effect of the epithelium, largely through PGE2 release, is removed.

Structural and functional study of control of canine tracheal smooth muscle

1980 ◽  
Vol 238 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
M. S. Kannan ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Sympathetic Nerves ◽  
Tracheal Smooth Muscle ◽  
Functional Study ◽  
Field Stimulation ◽  
Electron Microscopic ◽  
Microscopic Studies ◽  
Stimulation Of

The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.

Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O3 inhalation

1988 ◽  
Vol 65 (1) ◽  
pp. 57-64 ◽  
Author(s):  
G. L. Jones ◽  
P. M. O'Byrne ◽  
M. Pashley ◽  
R. Serio ◽  
J. Jury ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Chloride ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Trachealis Muscle

Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.

Temperature dependence of responses of esophageal smooth muscle to electrical field stimulation.

1977 ◽  
Vol 232 (4) ◽  
pp. E432
Author(s):  
D J De Carle ◽  
A C Szabo ◽  
J Christensen
Keyword(s):  
Smooth Muscle ◽  
Temperature Dependence ◽  
Electrical Field Stimulation ◽  
Ringer Solution ◽  
Current Strength ◽  
Field Stimulation ◽  
Electrical Field ◽  
Linear Decline ◽  
Temperature Amplitude ◽  
Stimulation Of

Strips of smooth muscle, cut transversely from the smooth-muscle segment of opossum esophagus, were superfused with oxygenated Krebs-Ringer solution at 37 degrees C in a system that allowed electrical field stimulation of the intrinsic nerves. Three-to-five-second trains of rectangular pulses (0.5 ms long at 10 Hz) were delivered at 30-s intervals at supramaximal maximal current strength. In strips from the esophageal body, each train resulted in a twitch which followed after the end of train with a particular latency, the off-response. Strips from the esophagogastric sphincter relaxed during the train. Temperature was varied above and below 37 degrees C to observe the temperature dependence of the responses. Latency of the off-response varied exponentially with temperature. Amplitude of the off-response showed a linear decline with changes in temperature, both above and below 35 degrees C, the zero-intercepts being 19.6 and 42.3 degrees C, respectively. Amplitude of relaxation of strips from the junction varied little between 20 and 37 degree C but declined sharply beyond those limits, the zero-intercepts being 14.2 and 42 degrees C, respectively.

The innervation of smooth muscle in the primary bronchus of the chicken

1980 ◽  
Vol 58 (3) ◽  
pp. 310-315 ◽  
Author(s):  
R. Bhatla ◽  
C. C. Ferguson ◽  
J. B. Richardson
Keyword(s):  
Smooth Muscle ◽  
Adrenergic Innervation ◽  
Primary Response ◽  
Cholinergic Innervation ◽  
Field Stimulation ◽  
Inhibitory System ◽  
Granular Vesicles ◽  
Adrenergic Blocking ◽  
Large Granular Vesicles

The innervation of the primary bronchus of the chicken was studied with in vitro pharmacological techniques and with the electron microscope. The primary response of the smooth muscle to field stimulation is relaxation of the muscle and this is not blocked by adrenergic blocking agents. Excitatory cholinergic innervation can be demonstrated when the muscle is partially relaxed. Examination of the ultrastructure of the muscle and nerves shows numerous axon profiles filled with large granular vesicles of the type associated with noradrenergic or purinergic neurotransmission. Agranular vesicles characteristic of cholinergic innervation are also seen but there is no evidence of adrenergic innervation to the smooth muscle. The smooth muscle ceils show connections of the nexus type. These findings indicate that the primary bronchus of the chicken has a dominant inhibitory system and this is nonadrenergic in type.

Stimulus-response relationships for isotonic shortening and isometric tension generation in rabbit trachealis

1994 ◽  
Vol 77 (4) ◽  
pp. 1638-1643 ◽  
Author(s):  
A. Opazo-Saez ◽  
P. D. Pare
Keyword(s):  
Smooth Muscle ◽  
Isometric Force ◽  
Electrical Field Stimulation ◽  
Isometric Tension ◽  
Maximal Response ◽  
Field Stimulation ◽  
Electrical Field ◽  
Increased Sensitivity ◽  
Isotonic Shortening

Nonspecific bronchial hyperresponsiveness in asthma is characterized by increased maximal airway narrowing (reactivity) and increased sensitivity of the airways. A decreased load on airway smooth muscle (ASM) has been suggested as a mechanism of increased reactivity. We hypothesized that decreased ASM load can also cause a leftward shift in the dose-response curve and explain increased sensitivity. We tested this hypothesis using rabbit tracheal smooth muscle strips in vitro by measuring isotonic shortening and isometric force during electrical field stimulation (1–100 Hz) at the length at which maximal active tension developed (Lmax), 90% Lmax, and 110% Lmax The frequency-response relationships expressed as frequency vs. percent maximal shortening or tension were not different at Lmax or 110% Lmax, but at 90% Lmax the frequency vs. shortening relationship was significantly shifted leftward relative to the frequency vs. tension relationship (P < 0.05). The electrical field stimulation frequencies that produced 50% maximal response for isometric tension and for isotonic shortening, respectively, were 6.7 +/- 1.9 and 3.9 +/- 0.7 Hz at 90% Lmax, 9.2 +/- 2.1 and 7.5 +/- 1.9 Hz at 100% Lmax, and 2.8 +/- 1.0 and 1.2 +/- 0.5 Hz at 110% Lmax. We conclude that, at lengths below Lmax, isotonic shortening is facilitated compared with isometric tension and therefore decreased ASM load in vivo may result in increased sensitivity.

P2Y1 receptors mediate inhibitory purinergic neuromuscular transmission in the human colon

2006 ◽  
Vol 291 (4) ◽  
pp. G584-G594 ◽  
Author(s):  
Diana Gallego ◽  
Pilar Hernández ◽  
Pere Clavé ◽  
Marcel Jiménez
Keyword(s):  
Smooth Muscle ◽  
Gastrointestinal Tract ◽  
Neuromuscular Transmission ◽  
Electrical Field Stimulation ◽  
Human Colon ◽  
Fast Component ◽  
Enteric Neurons ◽  
Field Stimulation ◽  
Electrical Field ◽  
Mrs 2179

Indirect evidence suggests that ATP is a neurotransmitter involved in inhibitory pathways in the neuromuscular junction in the gastrointestinal tract. The aim of this study was to characterize purinergic inhibitory neuromuscular transmission in the human colon. Tissue was obtained from colon resections for neoplasm. Muscle bath, microelectrode experiments, and immunohistochemical techniques were performed. 2′-deoxy- N6-methyl adenosine 3′,5′-diphosphate tetraammonium salt (MRS 2179) was used as a selective inhibitor of P2Y1 receptors. We found that 1) ATP (1 mM) and adenosine 5′-β-2-thiodiphosphate (ADPβS) (10 μM), a preferential P2Y agonist, inhibited spontaneous motility and caused smooth muscle hyperpolarization (about −12 mV); 2) MRS 2179 (10 μM) and apamin (1 μM) significantly reduced these effects; 3) both the fast component of the inhibitory junction potential (IJP) and the nonnitrergic relaxation induced by electrical field stimulation were dose dependently inhibited (IC50 ∼1 μM) by MRS 2179; 4) ADPβS reduced the IJP probably by a desensitization mechanism; 5) apamin (1 μM) reduced the fast component of the IJP (by 30–40%) and the inhibitory effect induced by electrical field stimulation; and 6) P2Y1 receptors were localized in smooth muscle cells as well as in enteric neurons. These results show that ATP or a related purine is released by enteric inhibitory motoneurons, causing a fast hyperpolarization and smooth muscle relaxation. The high sensitivity of MRS 2179 has revealed, for the first time in the human gastrointestinal tract, that a P2Y1 receptor present in smooth muscle probably mediates this mechanism through a pathway that partially involves apamin-sensitive calcium-activated potassium channels. P2Y1 receptors can be an important pharmacological target to modulate smooth muscle excitability.

Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle

1987 ◽  
Vol 63 (4) ◽  
pp. 1396-1400 ◽  
Author(s):  
J. Tamaoki ◽  
K. Sekizawa ◽  
P. D. Graf ◽  
J. A. Nadel
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Prostaglandin D2 ◽  
Base Line ◽  
Field Stimulation ◽  
Electrical Field ◽  
Adrenergic Antagonist

To determine whether prostaglandin D2 (PGD2) modulates cholinergic neurotransmission in airway smooth muscle and, if so, what the mechanism of action is, we studied bronchial segments from dogs under isometric conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle contraction, which was reduced after blockade of muscarinic receptors, so that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9 +/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05). Physostigmine, at a concentration insufficient to alter base-line tension (10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4 +/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2 increased the contractile response to electrical field stimulation (1–50 Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the response to administered acetylcholine was not affected by PGD2. On the other hand, PGD2-induced augmentation of the response to electrical field stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8% in the presence of physostigmine (10(-8) M) and was abolished by atropine but not affected by the alpha-adrenergic antagonist phentolamine or the histamine H1-blocker pyrilamine. These results suggest that the contraction of airway smooth muscle induced by PGD2 is in in part mediated by a cholinergic action and that PGD2 prejunctionally augments the parasympathetic contractile response, likely involving the accelerated release of acetylcholine at the neuromuscular junction.

Electrical stimulation causes endothelium-dependent relaxation in lung vessels

1983 ◽  
Vol 244 (6) ◽  
pp. H793-H798 ◽  
Author(s):  
G. W. Frank ◽  
J. A. Bevan
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Electrical Field Stimulation ◽  
Procaine Hydrochloride ◽  
Smooth Muscle Relaxation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Vessel Segment ◽  
Mechanical Removal

Ring segments of blood vessels were isolated from the lungs of rabbits, cats, and monkeys. After constriction with norepinephrine, electrical field stimulation caused smooth muscle relaxation in these segments. Mechanical removal of the endothelial layer, verified by scanning electron microscopy, abolished or greatly attenuated the relaxation. The response could be restored in part by apposing the endothelial surface of another vessel segment and the denuded inner surface of the constricted vessel segment. Incubation with tetrodotoxin, procaine hydrochloride, guanethidine, propranolol, atropine, metiamide, indomethacin, quinacrine hydrochloride, 5,8,11,14-eicosatetraynoic acid, aminophylline, and verapamil failed to block or enhance the relaxation response to field stimulation. We conclude that the vascular endothelium in the larger pulmonary arteries and veins studied contains a diffusible substance that inhibits smooth muscle contraction. Its release by electrical field stimulation in vitro does not involve classic neuronal transmitter release or metabolism of arachidonic acid by cyclooxygenase or lipooxygenase.

Effects of elastic loading on porcine trachealis muscle mechanics

1990 ◽  
Vol 69 (3) ◽  
pp. 1033-1039 ◽  
Author(s):  
K. Ishida ◽  
P. D. Pare ◽  
T. Blogg ◽  
R. R. Schellenberg
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Elastic Loading ◽  
Trachealis Muscle

To shorten in vivo, airway smooth muscle must overcome an elastic load provided by cartilage and lung parenchyma. We examined the effects of linear elastic loads (0.2-80 g/cm) on the active changes in porcine trachealis muscle length and tension in response to electrical field stimulation in vitro. Increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening while causing an increase in tension generation of muscle strips stimulated by electrical field stimulation. Shortening was decreased by 50% at a load of 8 g/cm. At small elastic loads (less than or equal to 1 g/cm) contractile responses approximated isotonic responses (shortening approximately 60% of starting length), whereas at large loads (20 g/cm) responses approximated isometric responses with minimal shortening (20%). We conclude that elastic loading significantly alters the mechanical properties of airway smooth muscle in vitro, effects that are likely relevant to the loads against which the smooth muscle must contract in vivo.

Sign in / Sign up

Export Citation Format

Share Document