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.

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.

Serotonin reuptake inhibitors fluoxetine and citalopram relax intestinal smooth muscle

2001 ◽  
Vol 79 (7) ◽  
pp. 580-584 ◽  
Author(s):  
Pal Pacher ◽  
Zoltan Ungvari ◽  
Valéria Kecskeméti ◽  
Tamás Friedmann ◽  
Susanna Furst
Keyword(s):  
Smooth Muscle ◽  
Serotonin Reuptake ◽  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Electrical Field Stimulation ◽  
Intestinal Smooth Muscle ◽  
Dependent Manner ◽  
Guinea Pig Ileum ◽  
Electrical Field ◽  
Concentration Dependent Manner

Selective serotonin reuptake inhibitor antidepressants (SSRIs) exert depressant effects on cardiac myocytes and vascular smooth muscle cells by inhibiting Ca2+ channels. We hypothesized that the SSRIs fluoxetine and citalopram affect the contractile activity of intestinal smooth muscle by interfering with Ca2+ entry and (or) signaling pathways. The effects of fluoxetine and citalopram on contractions of guinea-pig ileum longitudinal muscle-myenteric plexus preparations (LMMP) were compared with the effects of the voltage-operated Ca2+ channel inhibitors nifedipine and diltiazem. In a concentration-dependent manner, nifedipine, diltiazem, fluoxetine, and citalopram elicited relaxation of LMMPs contracted by electrical field stimulation (EC50 values of 4 × 10–7 M, 1.4 × 10–6 M, 1.4 × 10–5, and 6.8 × 10–6 M, respectively). Nifedipine, diltiazem, fluoxetine, and citalopram also relaxed LMMPs contracted with a depolarizing concentration of KCl (48 mM; EC50 values of 1.8 × 10–8 M, 1.4 × 10–7 M, 3.7 × 10–6 M, and 6.3 × 10–6, respectively), a response that could be reversed by increasing the extracellular Ca2+ concentration (2.5–30 mM). These data suggest that fluoxetine and citalopram elicit relaxation of intestinal smooth muscle, likely by inhibiting Ca2+ channel(s). This effect may be of clinical importance.Key words: fluoxetine (Prozac(r)), citalopram (Seropram(r)), nifedipine, diltiazem, L-type Ca2+ channels, intestinal smooth muscle.

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.

Bovine gallbladder muscularis: source of a myogenic receptor for cholecystokinin

1988 ◽  
Vol 254 (3) ◽  
pp. G294-G299 ◽  
Author(s):  
B. Schjoldager ◽  
M. J. Shaw ◽  
S. P. Powers ◽  
P. F. Schmalz ◽  
J. Szurszewski ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Neuronal Response ◽  
Electrical Field Stimulation ◽  
Adrenergic Blockade ◽  
Dependent Manner ◽  
Field Stimulation ◽  
Electrical Field ◽  
Concentration Dependent Manner ◽  
High Affinity

Despite being a classic target for the gastrointestinal peptide hormone, cholecystokinin (CCK), the gallbladder CCK receptor is not well characterized. Pharmacological studies of small species suggest that CCK action can be mediated by direct myogenic or by both myogenic and neurogenic receptors. To prepare for the biochemical characterization of a gallbladder CCK receptor and to define the subtype of the receptor being studied, we have performed autoradiographic localization and pharmacological characterization of CCK receptors on bovine gallbladder. Autoradiography demonstrated high-affinity specific CCK-binding sites only on the muscularis. CCK-8 stimulated tonic contraction of longitudinal strips of gallbladder muscularis in a concentration-dependent manner, with an ED50 of 0.2 nM. Antagonism at the cholinergic receptor with 1 microM atropine or axonal transmission with 1 microM tetrodotoxin did not modify CCK-induced contraction, supporting a direct myogenic effect of this hormone. Optimal electrical field stimulation (10 V, 10 Hz, 500 microseconds) to elicit a neuronal response resulted in muscle strip relaxation, which was abolished with adrenergic blockade (1 microM phentolamine, 1 microM propranolol). Although acetylcholine administration stimulated contraction, electrical field stimulation did not, even in the presence of phentolamine, propranolol, and/or CCK. Thus, in bovine gallbladder muscularis, there is evidence for a functional CCK receptor only on smooth muscle cells. Demonstration of a single, high-affinity specific CCK-binding site on an enriched plasma membrane preparation of bovine gallbladder muscularis is consistent with this representing a myogenic CCK receptor.

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.

Epithelial modulation of cholinergic responses in human tracheal smooth muscle

1994 ◽  
Vol 72 (3) ◽  
pp. 199-204
Author(s):  
Tony R. Bai ◽  
F. W. F. Prasad
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Isometric Tension ◽  
Tracheal Smooth Muscle ◽  
Maximal Response ◽  
Field Stimulation ◽  
Electrical Field ◽  
Paired Samples ◽  
Mechanical Removal ◽  
Specific Permeability

The aim of this study was to test the hypothesis that the increase in maximal responses to histamine, acetylcholine, and cholinergic electrical field stimulation and decreased relaxant responses to isoprenaline reported in asthmatic tracheal smooth muscle result from the epithelial damage observed in asthma. The effect of mechanical removal of the epithelium on contractile and relaxant responses was examined in normal human postmortem tracheal smooth muscle strips. The epithelium was removed from alternate tracheal strips obtained from 25 subjects within 14 h of sudden death from nonrespiratory causes. In paired samples, contractile cholinergic and inhibitory nonadrenergic, noncholinergic (i-NANC) neural responses to electrical field stimulation and responses to exogenous histamine, potassium chloride, theophylline, and isoprenaline were unaffected by removal of the epithelium. However, the maximal isometric tension (Tmax) induced by methacholine increased by 70.1 ± 19.8% (mean ± SE, p < 0.005, n = 9), without alteration in EC50. These data suggest that disruption of the epithelium is unlikely to be the explanation of the abnormalities observed in trachea in fatal asthma. Explanations of the increase in maximal response to methacholine following removal of the epithelium include loss of an epithelium-derived relaxant factor released via an epithelial muscarinic receptor or loss of a specific permeability or metabolic barrier imposed by the epithelium for methacholine.Key words: asthma, epithelium-derived relaxant factor, airway responsiveness, airway innervation.

Effect of bradykinin on airway neural responses in vitro

1992 ◽  
Vol 73 (4) ◽  
pp. 1537-1541 ◽  
Author(s):  
M. Miura ◽  
M. G. Belvisi ◽  
P. J. Barnes
Keyword(s):  
Matched Control ◽  
Electrical Field Stimulation ◽  
Dependent Manner ◽  
Field Stimulation ◽  
Neural Responses ◽  
Response Curves ◽  
Electrical Field ◽  
Concentration Dependent Manner ◽  
Before And After

We investigated the effects of bradykinin (BK) on airway excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic nerves in vitro. Neural responses were elicited by electrical field stimulation in guinea pig airways in vitro before and after the addition of BK (10(-10)-10(-7) M). Captopril (10(-5) M) and phosphoramidon (10(-6) M) were added to prevent degradation of BK, and all neural responses were measured in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M). BK potentiated e-NANC responses in bronchi in a concentration-dependent manner (10(-10)-10(-7) M) without changing concentration-response curves to exogenously applied substance P (10(-10)-10(-5) M). BK significantly potentiated e-NANC neural constrictor responses by 22 +/- 7% at 10(-8) M (mean +/- SE, n = 5, P < 0.05) and 32 +/- 7% at 10(-7) M (n = 8, P < 0.01), compared with changes in time-matched control tissues (7 +/- 2%, n = 8). The potentiation of e-NANC responses by BK was abolished by pretreatment with a specific B2-receptor antagonist, HOE 140 (10(-7) M). Cholinergic constrictor responses elicited to electrical field stimulation were not affected by the addition of BK (up to 10(-7) M). These results suggest that BK potentiates e-NANC bronchoconstrictor responses prejunctionally via a B2-receptor.

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