Epithelial modulation of preterm airway smooth muscle contraction

1993 ◽  
Vol 74 (3) ◽  
pp. 1437-1443 ◽  
Author(s):  
H. B. Panitch ◽  
M. R. Wolfson ◽  
T. H. Shaffer
Keyword(s):  
Mechanical Ventilation ◽  
Smooth Muscle ◽  
Preterm Infants ◽  
Airway Epithelium ◽  
Smooth Muscle Contraction ◽  
Airway Hyperreactivity ◽  
The Other ◽  
Maximal Response ◽  
Maximal Stress ◽  
Trachealis Muscle

To determine if epithelium from immature airways can modulate the responsiveness of smooth muscle, we studied paired trachealis muscle strips from preterm sheep. The epithelium was removed from one strip and left undisturbed in the other. Concentration-effect (CE) curves to acetylcholine (ACh), KCl, and isoproterenol were obtained. To evaluate maturational effects, responses to ACh and isoproterenol were studied in trachealis strips from adult airways. Maximal stress (Po) to ACh increased after epithelium removal in preterm (P < 0.05) but not adult strips. Epithelium removal caused a leftward shift of the ACh CE curves in both preterm and adult strips (P < 0.001) and a decrease in the dose required to achieve a one-half maximal response (ED50) in both preterm (P < 0.005) and adult strips (P < 0.05). The magnitude of the change in Po as well as in the ED50 for ACh between preterms and adults was similar. Epithelium removal did not alter either the Po or the CE curves of preterm strips stimulated by KCl. Response to isoproterenol in precontracted strips was enhanced in the presence of an intact epithelium in both groups (P < 0.05). These data demonstrate that preterm airway epithelium is able to modulate the responsiveness of smooth muscle. Additionally, the magnitude of the effect is unchanged with maturation. We speculate that damage of airway epithelium from mechanical ventilation may contribute to the increased incidence of airway hyperreactivity observed in preterm infants.

Modulation of smooth muscle contraction by sphingosylphosphorylcholine

1995 ◽  
Vol 269 (3) ◽  
pp. G370-G377 ◽  
Author(s):  
K. N. Bitar ◽  
H. Yamada
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
Mitogen Activated Protein Kinase ◽  
Maximal Response

We have investigated the effect of sphingosylphosphorylcholine (SPC), a synthetic product that was implicated in the sphingomyelin cycle, and have assessed its role in intracellular signaling. SPC induced a dose-dependent contractile effect of smooth muscle cells isolated from the rectosigmoid of the rabbit. Maximal contraction occurred at 10(-6) M. The response started early, 25.4 +/- 6% shortening at 15 s, peaked at 30 s (32.5 +/- 2%), and remained sustained at 8 min (30.0 +/- 3.5%). Preincubation of the cells with thapsigargin had no effect on contraction induced by SPC. The response to a combination of threshold concentrations of inositol 1,4,5-trisphosphate (IP3) and SPC was additive and was significantly different from the maximal response elicited by each agent alone. SPC also induced activation of mitogen-activated protein kinase (MAP kinase). This study demonstrates that SPC is important in cellular signaling of gastrointestinal smooth muscle cells through a mechanism that is independent of IP3-sensitive calcium release and probably through activation of a protein kinase C-mediated activation of MAP kinase.

scholarly journals Functional interrelationship between calponin and caldesmon

1991 ◽  
Vol 280 (1) ◽  
pp. 33-38 ◽  
Author(s):  
R Makuch ◽  
K Birukov ◽  
V Shirinsky ◽  
R Dabrowska
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Atpase Activity ◽  
Smooth Muscle Contraction ◽  
The Other ◽  
High Concentration ◽  
Thin Filaments ◽  
Actomyosin Atpase ◽  
Molar Excess ◽  
Low Concentrations

Calponin and caldesmon, constituents of smooth-muscle thin filaments, are considered to be potential modulators of smooth-muscle contraction. Both of them interact with actin and inhibit ATPase activity of smooth- and skeletal-muscle actomyosin. Here we show that calponin and caldesmon could bind simultaneously to F-actin when used in subsaturating amounts, whereas each one used in excess caused displacement of the other from the complex with F-actin. Calponin was more effective than caldesmon in this competition: when F-actin was saturated with calponin the binding of caldesmon was eliminated almost completely, whereas even at high molar excess of caldesmon one-third of calponin (relative to the saturation level) always remained bound to actin. The inhibitory effects of low concentrations of calponin and caldesmon on skeletal-muscle actomyosin ATPase were additive, whereas the maximum inhibition of the ATPase attained at high concentration of each of them was practically unaffected by the other one. These data suggest that calponin and caldesmon cannot operate on the same thin filaments. CA(2+)-calmodulin competed with actin for calponin binding, and at high molar excess dissociated the calponin-actin complex and reversed the calponin-induced inhibition of actomyosin ATPase activity.

Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro

1988 ◽  
Vol 65 (2) ◽  
pp. 914-920 ◽  
Author(s):  
K. J. Popovich ◽  
G. Sheldon ◽  
M. Mack ◽  
N. M. Munoz ◽  
P. Denberg ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Airway Epithelium ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Serotonin Antagonist

To elucidate mechanisms of platelet-activating factor (PAF)-induced contraction, we studied the effect of PAF on 203 canine tracheal smooth muscle (TSM) strips from 45 dogs in vitro in the presence and absence of platelets. PAF (10(-11) to 10(-7) M) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 x 10(5) platelets/microliter, PAF was an extremely potent contractile agonist (threshold 10(-11) M). This response was inhibited by the PAF antagonist, CV-3988 (10(-6) M), and reversed by the serotonin antagonist, methysergide (EC50 = 3.7 +/- 0.79 x 10(-9) M). Neither atropine nor chlorpheniramine (10(-9) to 10(-6) M) attenuated the response to PAF + platelets. In the presence of platelets, 10(-7) M PAF caused an increase in perfusate concentration of serotonin from 0.93 +/- 0.037 x 10(-8) to 1.7 +/- 0.046 x 10(-8) M (P less than 0.001). Tachyphylaxis, previously demonstrated to be irreversible, was shown to be a platelet-dependent phenomenon; contraction could be repeated in the same TSM after addition of fresh platelets. We demonstrate that PAF-induced contraction of canine TSM is caused by the release of cellular intermediates such as serotonin from platelets. We also demonstrate the site of PAF-induced tachyphylaxis in airway smooth muscle contraction.

Release of epithelium-derived relaxing factor after ozone inhalation in dogs

1988 ◽  
Vol 65 (3) ◽  
pp. 1238-1243 ◽  
Author(s):  
G. L. Jones ◽  
C. G. Lane ◽  
E. E. Daniel ◽  
P. M. O'Byrne
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Epithelium ◽  
Airway Hyperresponsiveness ◽  
The Other ◽  
Tracheal Epithelium ◽  
Control Group ◽  
Relaxing Factor

Airway epithelium has been reported to release epithelium-derived relaxing factor (EpDRF), which inhibits contraction of airway smooth muscle. This study tested the hypothesis that airway hyperresponsiveness after inhalation of ozone in dogs results from an inability to produce EpDRF. Two groups of five dogs each were studied; one group inhaled ozone, the other dry room air. Ozone-treated dogs developed airway hyperresponsiveness, whereas the control group did not. The acetylcholine provocative concentration decreased from 4.17 (%SE 1.35) to 0.56 mg/ml (%SE 1.24) (P = 0.0006) in the ozone-treated dogs and was 18.76 (%SE 2.04) and 29.77 mg/ml (%SE 2.07) in the air-treated dogs (P = 0.47). In vitro the presence of airway epithelium reduced the constrictor responses to acetylcholine, histamine, serotonin, and KCl in trachealis strips from the control dogs. This effect of epithelium was still present in trachealis strips from dogs with airway hyperresponsiveness. These results demonstrate that EpDRF is released from canine tracheal epithelium, that this function is not impaired in dogs with airway hyperresponsiveness after inhaled ozone, and that loss of EpDRF is not responsible for the development of airway hyperresponsiveness after inhaled ozone in dogs.

Role of endogenous NO in modulating airway contraction mediated by muscarinic receptors during development

1997 ◽  
Vol 273 (3) ◽  
pp. L531-L536 ◽  
Author(s):  
M. Jakupaj ◽  
R. J. Martin ◽  
I. A. Dreshaj ◽  
C. F. Potter ◽  
M. A. Haxhiu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptors ◽  
Airway Epithelium ◽  
Smooth Muscle Contraction ◽  
Tracheal Epithelium ◽  
Organ Bath ◽  
Response Curves ◽  
Before And After

We sought to characterize the role of endogenous nitric oxide (NO) released from airway epithelium in attenuating tracheal smooth muscle (TSM) contraction induced by exposure to acetylcholine (ACh). Organ bath experiments were performed on TSM from young pigs of three ages (3-7 days, 2-3 wk, and 3 mo). Concentration-response curves to cumulative doses of ACh (10(-8) to 10(-4) M) were generated before and after addition of the NO synthase blocker N omega-nitro-L-arginine methyl ester (L-NAME). L-NAME caused a significant increase in cholinergic sensitivity (decrease in 50% effective dose) at 3-7 days and 2-3 wk but not 3 mo. Maximum responses to ACh increased after L-NAME at all three ages. Removal of tracheal epithelium caused a significant increase in sensitivity to ACh at all ages, which progressively declined with advancing age. In the absence of epithelium, L-NAME no longer influenced contractile responses to ACh. Density of M3 muscarinic receptors in tracheal epithelium was upregulated in the youngest piglets. We conclude that, under in vitro conditions, release of endogenous NO opposes cholinergically induced contraction of piglet TSM. This phenomenon diminishes with advancing postnatal age, requires an intact airway epithelium, and correlates with upregulation of M3 muscarinic receptors in airway epithelium. We speculate that NO may play a useful role in attenuating cholinergically mediated airway smooth muscle contraction in early life when pulmonary function is characterized by high airway resistance.

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

1998 ◽  
Vol 84 (3) ◽  
pp. 809-814 ◽  
Author(s):  
Elisabeth M. Baile ◽  
Karen McKay ◽  
Lu Wang ◽  
Tony R. Bai ◽  
Peter D. Paré
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Vagal Stimulation ◽  
Smooth Muscle Contraction ◽  
Neural Responses ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Trachealis Muscle

Endogenous nitric oxide (NO) influences acetylcholine-induced bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response in several species. This study was designed to determine the importance of NO as a neurally derived modulator of ovine airway and bronchial vascular smooth muscle. We measured the response of pulmonary resistance (Rl) and bronchial blood flow (Q˙br) to vagal stimulation in 14 anesthetized, ventilated, open-chest sheep during the following conditions: 1) control; 2) infusion of the α-agonist phenylephrine to reduce baseline Q˙br by the same amount as would be produced by infusion of N ω-nitro-l-arginine (l-NNA), a NO synthase inhibitor; 3) infusion ofl-NNA (10−2 M); and 4) after administration of atropine (1.5 mg/kg). The results showed that vagal stimulation produced an increase in Rl andQ˙br in periods 1, 2, and 3( P < 0.01) that was not affected byl-NNA. After atropine was administered, there was no increase inQ˙br or Rl. In vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect ofl-NNA on neural relaxation but showed a complete blockade with propranolol ( P < 0.01). In conclusion, the vagally induced airway smooth muscle contraction and bronchial vascular dilation are not influenced by NO, and the sheep’s trachealis muscle, unlike that in several other species, does not have inhibitory nonadrenergic, noncholinergic innervation.

Histamine concentration and Ca2+ mobilization in arterial smooth muscle

1989 ◽  
Vol 257 (1) ◽  
pp. C122-C128 ◽  
Author(s):  
C. M. Rembold ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Extracellular Space ◽  
Smooth Muscle Contraction ◽  
Major Contributor ◽  
Histamine Concentration ◽  
Myosin Phosphorylation ◽  
Stress Development ◽  
Maximal Stress ◽  
Agonist Concentration ◽  
Rapid Generation

Smooth muscle contraction is dependent on Ca2+ entry from the extracellular space or release from intracellular stores. The sensitivity of these Ca2+ sources to agonist concentration was evaluated by measuring myoplasmic [Ca2+] (as estimated by aequorin), myosin phosphorylation, and isometric stress in the swine carotid media. High histamine concentrations produced transient elevations in [Ca2+] and phosphorylation with rapid generation of near maximal stress. Lower histamine concentrations produced much smaller [Ca2+] and phosphorylation transients, and stress development was slower. Peak [Ca2+] was proportional to the rate of stress development. Steady-state [Ca2+], phosphorylation, and stress values (which are dependent on extracellular Ca2+) were more sensitive to histamine concentration than was the peak [Ca2+] response both in the presence and absence of extracellular CaCl2 (measures of intracellular Ca2+ release). This result suggests that the mechanism for Ca2+ influx from the extracellular space is more sensitive to histamine than intracellular Ca2+ release. These results are also consistent with the hypothesis that agonist-releasable sarcoplasmic reticular Ca2+ is the major contributor to initial phosphorylation transients that enhance the rate of stress development.

Maturation of acetylcholinesterase expression in tracheal smooth muscle contraction

1990 ◽  
Vol 259 (2) ◽  
pp. L130-L135 ◽  
Author(s):  
R. W. Mitchell ◽  
T. M. Murphy ◽  
E. Kelly ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Maximal Response ◽  
Response Curves ◽  
Electrical Field ◽  
Stimulus Response ◽  
Cholinergic Contraction

We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from 21 2-wk-old swine (2ws) and 19 10-wk-old swine (10ws) were tethered isometrically at optimal resting length, and responses were expressed as percent of the maximum to 63 mM potassium-chloride (%KCl). Cumulative concentration-response curves to KCl were equivalent for TSM from 2 and 10ws. However, maximal contraction to ACh in 2ws (168 +/- 8.4 %KCl) was greater than for 10ws (142 +/- 2.3 %KCl; P less than 0.02). Stimulus-response curves (field electrodes; AC source) demonstrated greater sensitivity for TSM in 10ws (stimulus causing 50% of the maximal response = 3.32 +/- 0.13 V in 2ws vs. 2.25 +/- 0.12 V in 10ws; P less than 0.001), indicating that the greater cholinomimetic responsiveness of 2ws did not result from augmented presynaptic nerve conduction. The AChase inhibitor, physostigmine, caused 1) greater sensitivity of responses elicited by electrical field stimulation in 2ws (P less than 0.05) but not in 10ws (P = NS), 2) augmentation of maximal responses to exogenous ACh in 10ws (27% increase; P less than 0.01) but not 2ws (2% increase; P = NS), and 3) a greater increase in sensitivity to cholinomimetic activation in 2ws compared with 10ws (P less than 0.02). These data demonstrate increased cholinergic contraction of TSM in 2 vs. 10ws that results at least in part from reduced AChase activity in the trachea of immature animals.

Effect of PAF on parasympathetic contraction of canine airways

1989 ◽  
Vol 66 (6) ◽  
pp. 2629-2634 ◽  
Author(s):  
R. A. Bethel ◽  
S. P. Curtis ◽  
D. C. Lien ◽  
C. G. Irvin ◽  
G. S. Worthen ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Airway Hyperreactivity ◽  
Dependent Manner ◽  
Airway Edema ◽  
Potential Mediator ◽  
Lung Resistance ◽  
Trachealis Muscle ◽  
Dose Dependent

Platelet-activating factor (PAF) increases the bronchoconstrictor response of mammalian airways to cholinergic agonists and is thus implicated as a potential mediator of airway hyperreactivity. This study further defines the nature of the increase in airway responsiveness induced by PAF. We employed an in situ canine tracheal preparation, which allows differentiation of the effects PAF has on airway smooth muscle contraction from confounding effects it has on inducing airway edema and secretions. We found that PAF, infused regionally into tracheal arteries, increases the responsiveness of the trachealis muscle to parasympathetic stimuli in a dose-dependent manner. This effect occurred within 15 min. To determine whether the increase in trachealis muscle responsiveness resulted from effects localized to the trachea, we compared the effect of PAF on the tracheal segment with effects of the lower airways of the lung. Delivered to the arteries perfusing the tracheal segment, PAF did not increase lung resistance during vagus nerve stimulation. These data indicate that airway hyperresponsiveness elicited by PAF results from regional stimulation and/or release of mediators that augment tracheal contractility and that this effect is distinct from systemic effects elicited by PAF.

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