Differential tachykinin receptor subtype activation in capsaicin and KCl contractions of guinea pig trachealis

1995 ◽  
Vol 269 (6) ◽  
pp. L837-L842
Author(s):  
R. W. Mitchell ◽  
I. M. Ndukwu ◽  
A. Herrnreiter ◽  
K. Uzendoski ◽  
B. Gitter ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Receptor Subtype ◽  
Nk1 Receptor ◽  
Electrical Field ◽  
Tachykinin Receptor ◽  
Nk1 Receptor Antagonist

We assessed the role of endogenously secreted tachykinins in mediating contraction caused by potassium chloride (KCl) in guinea pig tracheal smooth muscle (TSM) strips in vitro. Maximal isometric contraction was elicited with approximately 45 mM KCl and was 196 +/- 8% of the response to electrical field stimulation (% EFS) in the same tissues. Muscarinic receptor blockade with atropine modestly attenuated this contraction caused by KCl to 175 +/- 9 %EFS (P < 0.05), and treatment with a selective neurokinin subtype 1 (NK1) receptor antagonist, LY-297911, caused even greater inhibition of KCl-elicited contraction to 124 +/- 8 %EFS (P < 0.001). By contrast, SR-48968, a selective NK2 antagonist, had no effect on contraction caused by KCl (183 +/- 9 %EFS; P = NS vs. KCl alone). However, given together at the same concentration, SR-48968 augmented the inhibition of contraction caused by LY-297911 to 93 +/- 15 %EFS (P < 0.05 vs. LY-297911 alone). In contrast to the effect on KCl-induced contraction, LY-297911 caused only moderate inhibition of the contraction caused by capsaicin to 81 +/- 13 %EFS (P < 0.05 vs. control, 114 +/- 15 %EFS), whereas SR-48968 caused substantial attenuation of contraction caused by capsaicin to 23 +/- 5 %EFS (P < 0.005 vs. LY-297911). We demonstrate that a significant portion of the contraction caused by KCl, in addition to capsaicin, is elicited in guinea pig TSM through neurokinin secretion. However, NK1 receptors predominantly mediate contraction caused by KCl, and NK2 receptors predominantly mediate contraction elicited by capsaicin in guinea pig airway smooth muscle.

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.

Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions

1999 ◽  
Vol 276 (5) ◽  
pp. G1243-G1250 ◽  
Author(s):  
Henry P. Parkman ◽  
Anthony P. Pagano ◽  
James P. Ryan
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Cholinergic Nerves ◽  
Ach Release ◽  
Electrical Field ◽  
And Function

The aim of this study was to determine the functional role of muscarinic receptor subtypes regulating gallbladder cholinergic contractions. Electrical field stimulation (EFS; 16 Hz) produced contractile responses of guinea pig gallbladder muscle strips in vitro that were inhibited by 1 μM tetrodotoxin (2 ± 2% of control) and 1 μM atropine (1 ± 1% of control), indicating activation of intrinsic cholinergic nerves. Exogenous ACh (5 μM)-induced contractions were inhibited by atropine (1 ± 1% of control) but not tetrodotoxin (102 ± 1% of control), indicating a direct effect on smooth muscle. The M1 receptor antagonist pirenzepine (10 nM) had no effect on ACh-induced contractions but inhibited EFS-induced contractions by 11 ± 3%. The M2 antagonist methoctramine (10 nM) had no effect on ACh-induced contractions but augmented EFS-induced contractions by 5 ± 2%. The M3 antagonist 4-DAMP (10 nM) inhibited ACh-induced contractions by 14 ± 4% and EFS-induced contractions by 22 ± 5%. In conclusion, specific M1, M2, and M3 receptors modulate gallbladder muscle contractions by regulating ACh release from cholinergic nerves and mediating the contraction. Cholinergic contractions are mediated by M3 receptors directly on the smooth muscle. M2 receptors are on cholinergic nerves and function as prejunctional inhibitory autoreceptors. M1 receptors are on cholinergic nerves and function as prejunctional facilitatory autoreceptors.

Effect of airway inflammation on smooth muscle shortening and contractility in guinea pig trachealis

1993 ◽  
Vol 265 (6) ◽  
pp. L549-L554 ◽  
Author(s):  
R. W. Mitchell ◽  
I. M. Ndukwu ◽  
K. Arbetter ◽  
J. Solway ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Neurogenic Inflammation ◽  
Isometric Force ◽  
Electrical Field Stimulation ◽  
Shortening Velocity ◽  
Lever System ◽  
Force Velocity

We studied the effect of either 1) immunogenic inflammation caused by aerosolized ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity relationships were determined for nine epithelium-intact TSM strips from ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls. Muscle strips were tethered to an electromagnetic lever system, which allowed isotonic shortening when load clamps [from 0 to maximal isometric force (Po)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18 V). Optimal length for each muscle was determined during equilibration. Maximal shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s) compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/- 0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/- 0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We demonstrate Vmax and delta max are augmented in TSM after ovalbumin sensitization; in contrast, neurogenic inflammation caused by capsaicin has no effect on isolated TSM contractility in vitro. These data suggest that airway hyperresponsiveness in vivo that occurs in association with immunogenic or neurogenic inflammation may result from different effects of these types of inflammation on airway smooth muscle.

Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness

1986 ◽  
Vol 70 (6) ◽  
pp. 571-575 ◽  
Author(s):  
Christopher Murlas
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Physiological Salt Solution ◽  
Induced Responses ◽  
Field Stimulation ◽  
Electrical Field ◽  
Airway Mucosa

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C. 2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed. 3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh. 4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium. 5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.

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.

Role of the epithelium in airway smooth muscle responses to relaxant agonists

1991 ◽  
Vol 71 (4) ◽  
pp. 1434-1440 ◽  
Author(s):  
J. N. Yang ◽  
W. Mitzner ◽  
C. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Diffusion Barrier ◽  
Tracheal Wall ◽  
Maximal Effect ◽  
Direct Measurements ◽  
Dose Dependent ◽  
Muscle Responses

We studied the role of the guinea pig tracheal epithelium in modulating tracheal smooth muscle responses to the relaxant agonists albuterol, sodium nitroprusside, and theophylline. We used an in vitro preparation that allowed separation of the fluids bathing the luminal (internal) and serosal (external) surfaces of the trachea, and bronchodilators were administered to either surface of carbachol-contracted tracheae. All three drugs produced dose-dependent relaxation. However, albuterol and nitroprusside were less potent (concentration that produced half-maximal effect increased by 100- and 32-fold, respectively) when given to the epithelial side with the epithelium intact compared with the epithelium denuded or compared with serosal administration with the epithelium intact. These differences were not observed for theophylline, where smooth muscle responses were independent of either the side of stimulation or of the presence or absence of the epithelium. Direct measurements of the diffusion of theophylline across the tracheal wall in the presence or absence of epithelium showed that after 5 h of incubation with a fixed luminal concentration of theophylline, only 1.7% had diffused across the tracheal wall with the epithelium intact. This increased to only approximately 3.3% when the epithelium was denuded. These results suggest that the epithelial is a relatively weak barrier for lipophilic agents but has a major role as a diffusion barrier to hydrophilic substances.

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.

Lack of effect of botulinum toxin on nonadrenergic, noncholinergic inhibitory responses of the guinea pig fundus in vitro

1980 ◽  
Vol 58 (1) ◽  
pp. 88-92 ◽  
Author(s):  
M. L. Paul ◽  
M. A. Cook
Keyword(s):  
Botulinum Toxin ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Cholinergic Nerves ◽  
Electrical Field

The nonadrenergic, noncholinergic inhibitory (NAI) response of guinea pig fundic strip to electrical field stimulation was examined in the presence of botulinum toxin and tetrodotoxin. Tetrodotoxin completely abolished the NAI response while botulinum toxin did not alter it. It is concluded that the mediator of NAI responses is unlikely to be released with acetylcholine from cholinergic nerves or that such release would have to occur by a mechanism resistant to botulinum toxin.

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