The signaling of amitriptyline-induced inhibitory effect on electrical field stimulation response in colon smooth muscle

AbstractThe aim of the study was to determine pathways involved in contraction and relaxation of the mouse urinary bladder. Mouse bladder strips were set up in gassed Krebs-bicarbonate solution and responses to various drugs and electrical field stimulation were obtained. Isoprenaline (b-receptor agonist) caused a 63% inhibition of carbachol precontracted detrusor (EC50=2nM). Carbachol caused contraction (EC50=0.3µM), responses were antagonised more potently by 4-DAMP (M3-antagonist) than methoctramine (M2-antagonist). Electrical field stimulation caused contraction, which was inhibited by atropine (60%) and less by guanethidine and α,β-methylene-ATP. The neurogenic responses were not potentiated by inhibition of nitric oxide synthase. Presence of an intact urothelium significantly depressed responses to carbachol (p=0.02) and addition of indomethacin and L-NNA to remove prostaglandin and nitric oxide production respectively did not prevent the inhibitory effect of the urothelium. In conclusion, b-receptor agonists cause relaxation and muscarinic agonists cause contraction via the M3-receptor. Acetylcholine is the main neurotransmitter causing contraction while nitric oxide has a minor role. The mouse and human urothelium are similar in releasing a factor that inhibits contraction of the detrusor muscle which is unidentified but is not nitric oxide or a prostaglandin. Therefore, the mouse may be used as a model to study the lower urinary tract.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.274.2.l220 ◽

1998 ◽

Vol 274 (2) ◽

pp. L220-L225 ◽

Cited By ~ 4

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.

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Control of neurotransmission by prostaglandins in canine trachealis smooth muscle

Journal of Applied Physiology ◽

10.1152/jappl.1984.57.1.129 ◽

1984 ◽

Vol 57 (1) ◽

pp. 129-134 ◽

Cited By ~ 90

Author(s):

E. H. Walters ◽

P. M. O'Byrne ◽

L. M. Fabbri ◽

P. D. Graf ◽

M. J. Holtzman ◽

...

Keyword(s):

Smooth Muscle ◽

Prostaglandin E2 ◽

Electrical Field Stimulation ◽

Tracheal Smooth Muscle ◽

Dependent Manner ◽

Field Stimulation ◽

Electrical Field ◽

Similar Time ◽

Concentration Dependent Manner ◽

Contractile Responses

Contractile responses of canine tracheal smooth muscle to electrical field stimulation diminished over a 2-h period of incubation. However, addition of indomethacin (10(-5) M) for a similar time not only prevented this inhibition of contractile response, but actually markedly increased the response to electrical field stimulation, suggesting that prostaglandins were responsible for the time-dependent inhibition. Measured prostaglandin E2 increased in the tissue bath over 2 h in control tissues. Addition of prostaglandin E2 to the tissue produced similar inhibition of contractile responses to electrical field stimulation in a concentration-dependent manner. In contrast, incubation alone, treatment with indomethacin, or addition of prostaglandin E2 had little, if any, effect on contractions induced by acetylcholine. We conclude that the release of prostaglandins from canine tracheal smooth muscle that occurs with time has a predominantly inhibitory effect on cholinergic neurotransmission at a prejunctional site.

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Relaxation and inhibition of contractile response to electrical field stimulation by Beraprost sodium in canine airway smooth muscle

Prostaglandins ◽

10.1016/0090-6980(93)90113-l ◽

1993 ◽

Vol 45 (4) ◽

pp. 363-373 ◽

Cited By ~ 18

Author(s):

J. Tamaoki ◽

A. Chiyotani ◽

K. Takeyama ◽

F. Yamauchi ◽

E. Tagaya ◽

...

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Contractile Response ◽

Electrical Field Stimulation ◽

Field Stimulation ◽

Electrical Field ◽

Beraprost Sodium

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

Clinical Science ◽

10.1042/cs0700571 ◽

1986 ◽

Vol 70 (6) ◽

pp. 571-575 ◽

Cited By ~ 32

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.

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Nonadrenergic inhibitory nervous system in human airways

Journal of Applied Physiology ◽

10.1152/jappl.1976.41.5.764 ◽

1976 ◽

Vol 41 (5) ◽

pp. 764-771 ◽

Cited By ~ 234

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.

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Nonadrenergic inhibitory nerves attenuate neurally mediated contraction in cat bronchi

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.5.1594 ◽

1990 ◽

Vol 69 (5) ◽

pp. 1594-1598 ◽

Cited By ~ 3

Author(s):

T. Aikawa ◽

K. Sekizawa ◽

S. Itabashi ◽

H. Sasaki ◽

T. Takishima

Keyword(s):

Contractile Response ◽

Stimulus Frequency ◽

Electrical Field Stimulation ◽

Inhibitory Effect ◽

Field Stimulation ◽

Inhibitory Effects ◽

Electrical Field ◽

Calcitonin Gene ◽

Contraction And Relaxation ◽

Biphasic Responses

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.

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Smooth muscle and neural mechanisms contributing to the downregulation of neonatal rat spontaneous bladder contractions during postnatal development

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00779.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. R2100-R2112 ◽

Cited By ~ 21

Author(s):

Yuen-Keng Ng ◽

William C. de Groat ◽

Hsi-Yang Wu

Keyword(s):

Smooth Muscle ◽

Postnatal Development ◽

Electrical Field Stimulation ◽

Bk Channels ◽

Bk Channel ◽

Neonatal Rat ◽

Field Stimulation ◽

Electrical Field ◽

Frequency Pattern ◽

Rat Urinary Bladder

Spontaneous bladder contractions (SBCs) in the neonatal rat urinary bladder change from a high-amplitude, low-frequency pattern to a low-amplitude, high-frequency pattern during the first 6 wk of life. Understanding the mechanism of this developmental change may provide insights into the causes of bladder overactivity in adults. In vitro whole bladder preparations from Sprague-Dawley rats were used to study the modulation of SBCs by calcium-activated potassium channels (KCa) and electrical field stimulation from 3 days to 6 wk of life. SBCs in 3-day-old bladders were unmasked by treatment with iberiotoxin (100 nM), an inhibitor of large conductance KCa (BK) channels, or apamin (100 nM), an inhibitor of small conductance KCa (SK) channels. Iberiotoxin significantly increased the magnitude of SBCs at 2–3 wk, whereas apamin was only effective at 6 wk. In 1–2 wk bladders, exposure to room temperature Krebs solution decreased SBCs. This decrease was reversed by activating intramural nerves with electrical field stimulation. The effect of electrical field stimulation was inhibited by atropine (1 μM), suramin (10 μM), or pretreatment with tetrodotoxin (1 μM) but was not reversed by tetrodotoxin applied after electrical field stimulation. BK-α mRNA increased threefold, and BK-α protein increased fivefold from 3 days to 6 wk. These data suggest that BK channels play an important role in the regulation of SBCs in the neonatal bladder and that both increased BK channel activity, as well as changes in smooth muscle sensitivity to locally released neurotransmitters contribute to the downregulation of SBCs during early postnatal development.

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