Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea

1987 ◽  
Vol 63 (4) ◽  
pp. 1401-1405 ◽  
Author(s):  
K. Sekizawa ◽  
J. Tamaoki ◽  
J. A. Nadel ◽  
D. B. Borson
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Response Curve ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Field Stimulation ◽  
Electrical Field ◽  
Contractile Responses ◽  
Cholinergic Neurotransmission

To determine the role of endogenous enkephalinase (EC 3.4.24.11) in regulating peptide-induced contraction of airway smooth muscle, we studied the effect of the enkephalinase inhibitor, leucine-thiorphan (Leu-thiorphan), on responses of isolated ferret tracheal smooth muscle segments to substance P (SP) and to electrical field stimulation (EFS). Leu-thiorphan shifted the dose-response curve to SP to lower concentrations. Atropine or the SP antagonist [D-Pro2,D-Trp7,9]SP significantly inhibited SP-induced contractions in the presence of Leu-thiorphan. Leu-thiorphan increased the contractile responses to EFS dose dependently, an effect that was significantly inhibited by the SP antagonist [D-Pro2,D-Trp7,9]SP. SP, in a concentration that did not cause contraction, increased the contractile responses to EFS. This effect was augmented by Leu-thiorphan dose dependently and was not inhibited by hexamethonium or by phentolamine but was inhibited by atropine. Because contractile responses to acetylcholine were not significantly affected by SP or by Leu-thiorphan, the potentiating effects of SP were probably on presynaptic-postganglionic cholinergic neurotransmission. Captopril, bestatin, or leupeptin did not augment contractions, suggesting that enkephalinase was responsible for the effects. These results suggest that endogenous tachykinins modulate smooth muscle contraction and endogenous enkephalinase modulates contractions produced by endogenous or exogenous tachykinins and tachykinin-induced facilitation of cholinergic neurotransmission.

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.

Control of neurotransmission by prostaglandins in canine trachealis smooth muscle

1984 ◽  
Vol 57 (1) ◽  
pp. 129-134 ◽  
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.

Hydrogen peroxide-induced potentiation of contractile responses in isolated rat airways

1990 ◽  
Vol 258 (4) ◽  
pp. L232-L237 ◽  
Author(s):  
J. L. Szarek ◽  
N. L. Schmidt
Keyword(s):  
Hydrogen Peroxide ◽  
Smooth Muscle ◽  
Electrical Stimulation ◽  
Airway Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Airway Hyperreactivity ◽  
Field Stimulation ◽  
Electrical Field ◽  
Contractile Responses ◽  
Isolated Rat

We hypothesized that metabolites of O2 may play a role in the development of airway hyperreactivity and undertook this study to examine the effects of one of these metabolites, hydrogen peroxide (H2O2), on electrical field stimulation-induced contractile responses of isolated rat intrapulmonary bronchi. Exposure to H2O2 (1 mM) elicited a transient contractile response with a peak response equivalent to 18.1 +/- 2.0% of the reference contraction obtained to electrical stimulation. The H2O2-induced contraction was attenuated by pretreatment of tissues with indomethacin and superoxide dismutase, but abolished by catalase and mianserin. Subsequent to H2O2 exposure, electrical field stimulation-induced contractile responses were potentiated (P less than 0.0001), whereas acetylcholine-induced contractions were not. The potentiating effects of H2O2 were inhibited by catalase and mianserin. Addition of 5-hydroxytryptamine (5-HT) to the bath similarly potentiated contractions to electrical stimulation (P less than 0.0001). Together, these results are consistent with a role for 5-HT in H2O2-induced contraction and the subsequent potentiation of airway smooth muscle contraction elicited by cholinergic nerve activation. Thus endogenous metabolites of O2 may be important in modulating airway smooth muscle tone.

Effect of hyperoxia on substance P expression and airway reactivity in the developing lung

1997 ◽  
Vol 273 (1) ◽  
pp. L40-L45 ◽  
Author(s):  
F. H. Agani ◽  
N. T. Kuo ◽  
C. H. Chang ◽  
I. A. Dreshaj ◽  
C. F. Farver ◽  
...  
Keyword(s):  
Substance P ◽  
Electrical Field Stimulation ◽  
Postnatal Life ◽  
Field Stimulation ◽  
Nk1 Receptor ◽  
Cholinergic Stimulation ◽  
Airway Reactivity ◽  
Electrical Field ◽  
Contractile Responses

This study was undertaken to characterize changes in the tachykinin system induced by hyperoxic exposure and the potential effects on airway contractile responses. We exposed 7-day-old rat pups to either room air or hyperoxia (> 95% O2) for 7 days to assess pulmonary beta-preprotachykinin (beta-PPT) gene expression, substance P (SP) levels, and airway contractile responses to cholinergic stimulation before and after neurokinin-1 (NK1) receptor blockade. Lung beta-PPT mRNA expression, lung and tracheal SP levels, and contractile responses to exogenous acetylcholine and electrical field stimulation were measured in vitro in normoxia- and hyperoxia-exposed tracheal cylinders. Hyperoxia caused a 1.1- to 2.6-fold increase in steady-state lung beta-PPT mRNA and a 50 and 32% increase in SP levels of lung and trachea, respectively. In response to cholinergic stimulation, maximal contractile force (Emax) of hyperoxia exposed tracheal muscle was significantly higher than for normoxic controls. Addition of the SP (NK1) receptor blocker CP-99994 (10 microM) decreased sensitivity to electrical field stimulation in both hyperoxic and normoxic trachea without a significant decline in Emax. These data provide evidence for both increased SP production and enhanced maximal contractile responses of hyperoxia-exposed neonatal trachea to cholinergic stimulation. The tachykinin peptide SP does not, however, appear to play a major role in the enhanced airway reactivity associated with hyperoxic lung injury during early postnatal life.

Contribution of Cav1.2 Ca2+ channels and store-operated Ca2+ entry to pig urethral smooth muscle contraction

2020 ◽  
Vol 318 (2) ◽  
pp. F496-F505
Author(s):  
Benjamin E. Rembetski ◽  
Kenton M. Sanders ◽  
Bernard T. Drumm
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Isometric Tension ◽  
Electrical Field ◽  
Voltage Dependent ◽  
Urethral Smooth Muscle ◽  
Evoked Contractions ◽  
Ca2 Channels

Urethral smooth muscle (USM) generates tone to prevent urine leakage from the bladder during filling. USM tone has been thought to be a voltage-dependent process, relying on Ca2+ influx via voltage-dependent Ca2+ channels in USM cells, modulated by the activation of Ca2+-activated Cl− channels encoded by Ano1. However, recent findings in the mouse have suggested that USM tone is voltage independent, relying on Ca2+ influx through Orai channels via store-operated Ca2+ entry (SOCE). We explored if this pathway also occurred in the pig using isometric tension recordings of USM tone. Pig USM strips generated myogenic tone, which was nearly abolished by the Cav1.2 channel antagonist nifedipine and the ATP-dependent K+ channel agonist pinacidil. Pig USM tone was reduced by the Orai channel blocker GSK-7975A. Electrical field stimulation (EFS) led to phentolamine-sensitive contractions of USM strips. Contractions of pig USM were also induced by phenylephrine. Phenylephrine-evoked and EFS-evoked contractions of pig USM were reduced by ~50–75% by nifedipine and ~30% by GSK-7975A. Inhibition of Ano1 channels had no effect on tone or EFS-evoked contractions of pig USM. In conclusion, unlike the mouse, pig USM exhibited voltage-dependent tone and agonist/EFS-evoked contractions. Whereas SOCE plays a role in generating tone and agonist/neural-evoked contractions in both species, this dominates in the mouse. Tone and agonist/EFS-evoked contractions of pig USM are the result of Ca2+ influx primarily through Cav1.2 channels, and no evidence was found supporting a role of Ano1 channels in modulating these mechanisms.

scholarly journals Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea

2001 ◽  
Vol 91 (1) ◽  
pp. 371-378 ◽  
Author(s):  
Zhong-Xin Wu ◽  
David F. Maize ◽  
Brian E. Satterfield ◽  
David G. Frazer ◽  
Jeff S. Fedan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Electrical Field Stimulation ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Field Stimulation ◽  
Electrical Field ◽  
Cholinergic Agonists ◽  
Airway Responses

Exposure to ozone (O3) enhances airway responsiveness, which is mediated partly by the release of substance P (SP) from airway neurons. In this study, the role of intrinsic airway neurons in O3-induced airway responses was examined. Ferrets were exposed to 2 ppm O3 or air for 1 h. Reactivity of isolated tracheal smooth muscle to cholinergic agonists was significantly increased after O3 exposure, as were contractions to electrical field stimulation at 10 Hz. Pretreatment with CP-99994, a neurokinin type 1 receptor antagonist, partially abolished the O3-induced reactivity to cholinergic agonists and electrical field stimulation. The O3-enhanced airway responses were present in tracheal segments cultured for 24 h, a procedure shown to deplete sensory nerves while maintaining viability of intrinsic airway neurons, and all the enhanced smooth muscle responses were also diminished by CP-99994. Immunocytochemistry showed that the percentage of SP-containing neurons in longitudinal trunk and the percentage of neurons innervated by SP-positive nerve fibers in superficial muscular plexus were significantly increased at 1 h after exposure to O3. These results suggest that enhanced SP levels in airway ganglia contribute to O3-induced airway hyperresponsiveness.

Nitric oxide as modulator of cholinergic neurotransmission in gastric muscle of rabbits

1997 ◽  
Vol 273 (2) ◽  
pp. G456-G463 ◽  
Author(s):  
M. C. Baccari ◽  
C. Iacoviello ◽  
F. Calamai
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Substance P ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Prostaglandin F2 Alpha ◽  
Fast Relaxation ◽  
Gastric Muscle ◽  
Relaxant Response

The effects of the nitric oxide (NO) synthesis inhibitors, NG-nitro-L-arginine (L-NNA) and NG-nitro-L-arginine methyl ester (L-NAME), on the electrical field stimulation (EFS)-induced inhibitory responses were investigated. EFS caused, in strips contracted by means of substance P (SP), prostaglandin F2 alpha (PGF2 alpha), or carbachol (CCh), a fast relaxant response that, depending on stimulation frequency and strip tension, could be followed by a slower, sustained relaxation. The NO synthesis inhibitors blocked the EFS-induced fast relaxations and often reversed them into contractions; these effects were greatly counteracted in SP- or PGF2 alpha-treated strips by scopolamine or atropine. In CCh-precontracted strips, either L-NNA or L-NAME became progressively unable to block the EFS-induced fast relaxations as the CCh concentration was increased. The NO synthesis inhibitors greatly reduced the sustained relaxant responses elicited either by EFS or exogenous vasoactive intestinal polypeptide (VIP). The results indicate that the NO synthesis inhibitors abolish the neurally induced fast relaxation by interfering with the cholinergic excitatory pathway. The involvement of both VIP and NO in sustained relaxations is also suggested.

Sign in / Sign up

Export Citation Format

Share Document