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PubMed1998

Drug-specific effects of volatile anesthetics on Ca2+ sensitization in airway smooth muscle.

UNLABELLED: Halothane directly relaxes airway smooth muscle, partly by decreasing the Ca2+ sensitivity during membrane receptor stimulation. The effects of other volatile anesthetics on Ca2+ sensitivity are unclear. In the current study, we compared the ability of halothane, sevoflurane, and isoflurane to inhibit increases in Ca2+ sensitivity during muscarinic receptor stimulation. Beta-escin-permeabilized canine tracheal smooth muscle strips were used. Anesthetics were applied during contractions induced by 3 microM acetylcholine and 10 microM guanosine 5'-triphosphate at a constant cytosolic Ca2+ concentration of 0.3 microM. Effects were evaluated as a percent relaxation from initial force corrected for time. Halothane significantly decreased force at both low (0.76 minimum alveolar anesthetic concentration [MAC]) and high (1.8 MAC) concentrations in a concentration-dependent manner. Sevoflurane also decreased force, significantly so at a high concentration (1.7 MAC). Isoflurane did not significantly affect force even at a high concentration (1.7 MAC). Halothane's relaxing effect was significantly greater than that of the other two anesthetics at each corresponding MAC concentration. Among these three volatile anesthetics compared at equipotent anesthetic concentrations, halothane was the most potent in reducing Ca2+ sensitivity during muscarinic receptor stimulation in canine tracheal smooth muscle. This may contribute to halothane's greater relaxing effect compared with isoflurane at the same MAC concentrations in intact airway smooth muscle. IMPLICATIONS: In this study, we showed that three volatile anesthetics (halothane, sevoflurane, and isoflurane) compared at equipotent anesthetic concentrations differed in their ability to inhibit Ca2+ sensitivity during muscarinic receptor stimulation in airway smooth muscle. The potency order was halothane > sevoflurane > or = isoflurane.

Acetylcholine↗
PubMed1986

Evidence for the presence of phospholamban in the endoplasmic reticulum of smooth muscle.

In microsomal vesicles isolated from several smooth muscles many polypeptides were phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase. In pig stomach and in rabbit and dog aorta components of Mr 22,000 and 11,000 were identified as forms of phospholamban. These polypeptides were, however, not observed in pig aorta. These phospholamban-like polypeptides presented the same electrophoretic mobility in sodium dodecyl sulphate gels as cardiac phospholamban, and the 22,000 Mr form showed a similar reaction to heat treatment in sodium dodecyl sulphate. Antibodies against purified canine cardiac phospholamban cross-reacted with the 22,000 and 11,000 Mr phosphorylatable polypeptides from smooth muscle membranes. Subcellular fractionation of porcine stomach smooth muscle indicated that phospholamban was present in the membranes of the endoplasmic reticulum and not in the plasma membranes. Phospholamban was also phosphorylated by an endogenous calcium-calmodulin-dependent protein kinase and by an endogenous cyclic AMP-dependent kinase. It is concluded that the endoplasmic reticulum of many, but possibly not all, smooth muscles contains phospholamban. However, the physiological role of phospholamban in smooth muscle remains to be established.

Animals↗
PubMed1990

Spatial dynamics of intracellular calcium in agonist-stimulated vascular smooth muscle cells.

Vasoconstrictor agonists stimulate smooth muscle contraction by inducing a rise in intracellular free Ca2+. Digital-imaging microscopy of fura-2 fluorescence from single vascular smooth muscle cells cultured from the human internal mammary artery has allowed us to record the subcellular alterations in Ca2+ that occur immediately after stimulation by receptor agonists. The thrombin-induced rise in cytoplasmic free Ca2+ begins in a discrete region typically located close to the end of the cell. Subsequently, this region of elevated Ca2+ expands until Ca2+ is elevated throughout the cell cytoplasm. The rate of spreading in the region of elevated Ca2+ in a linear direction averaged 10.1 microns/s, enabling it to traverse the length of most cells within approximately 5 s, and involved rises in Ca2+ of between 200 and 500 nM. In some cells, the Ca2+ rise began at both ends and collided midway. Similar dynamic changes in the spatial distribution of Ca2+ were recorded in cells stimulated by acetylcholine. The novel observation that vasoconstrictor agonists induce an elevation of Ca2+ in a localized region which subsequently expands throughout the cytoplasm of single smooth muscle cells may provide new insight into the nature of Ca2+ signaling in vascular tissue.

Acetylcholine↗
PubMed1986

Orientation response of arterial smooth muscle cells to mechanical stimulation.

Arterial smooth muscle cells from rabbit aortic media in primary culture and subculture were grown on hydrophilized and collagen-coated silicone membranes which were then subjected to cyclic and directional stretches and relaxations at a frequency of 60 times/min. The membranes were stretched with various amplitudes ranging from 2% to 20%. Smooth muscle cells on unstretched membranes in the same incubation chamber served as controls. In long-term experiments the stretching and relaxing of the membranes was continued for several days. While the smooth muscle cells grown on unstretched membranes remained in random orientation in all experiments, the cells which underwent mechanical stimulation showed a high degree of orientation. The angle of cell orientation varied in direct relation to the stretching amplitude and became steeper in correlation to the intensity of the mechanical stimulus. The angle of cell orientation was reversible, as preoriented cells changed their orientation when another stretching amplitude was applied. To study the role of cytoskeleton in the process of cell orientation, we examined the behaviour of the intracellular actin filament system. In short-term experiments the smooth muscle cells were exposed for 3 to 12 h to cyclic and directional stretches and relaxations with an amplitude of 10%. We observed a rearrangement of the intracellular actin filament system prior to the orientation of the whole cell bodies. The present study provides evidence that stretching the artery wall by blood pulsation may result in an orientation response of the intracellular actin cytoskeleton and in the orientation of the smooth muscle cells within the media of artery walls.

Actins↗
PubMed2001

[Effect of unprepared and prepared "he zi" on contraction of isolated trachea smooth muscle in rabbits].

Isolated trachea smooth muscle in rabbits induced by Ach or KCl was adopted to study the effect of unprepared and prepared "He Zi". The results showed that unprepared "He Zi" couldn't affect the contraction of isolated trachea smooth muscle in rabbit induced by Ach or KCl, and that prepared "He Zi" couldn't affect the contraction of isolated trachea smooth muscle in rabbit induced by KCl. The results also showed that prepared "He Zi" could significantly inhibit the contraction induced by Ach. The inhibition effect may not be associated with cGMP, adrenergic receptor, and release of NO and prostaglandin, and was epithelium independent. Maybe the different content of tannic acid contributed to the different effect between unprepared and prepared "He Zi".

Acetylcholine↗
PubMed2005

Stretch-dependent growth and differentiation in vascular smooth muscle: role of the actin cytoskeleton.

The smooth muscle cells in the vascular wall are constantly exposed to distending forces from the intraluminal pressure. A rise in blood pressure triggers growth of the vessel wall, which is characterized primarily by hypertrophy of smooth muscle cells with maintained differentiation in a contractile phenotype. Growth factor stimulation of dissociated smooth muscle cells, on the other hand, causes proliferative growth with loss of contractility. This type of response is also found in neointima development following angioplasty and in atherosclerotic lesions. An intact tissue environment is therefore critical for preserved differentiation. Recent advances point to a role of actin polymerization in the expression of smooth muscle differentiation marker genes, in concert with serum response factor (SRF) and cofactors, such as myocardin. Stretch of intact venous smooth muscle activates Rho and inhibits the actin filament severing factor cofilin, resulting in increased actin polymerization. Concomitantly, the rates of synthesis of SRF-regulated differentiation markers, such as SM22alpha, calponin, and alpha-actin, are increased. This increase in differentiation signals is parallel with activation of the mitogen-activated protein (MAP) kinase pathway. Thus stretch-induced growth in a maintained contractile phenotype occurs by dual activation of signal pathways regulating both growth and differentiation. A current challenge is to identify sites of crosstalk between these pathways in intact smooth muscle tissue.

Actins↗
PubMed1989

Smooth muscle gelsolin and a Ca2+-sensitive contractile cell model.

Smooth muscle gelsolin, termed smooth muscle 90-kDa protein in our previous paper (Kanno et al. FEBS Lett. 1985; 184:202-206), was purified from bovine aorta. Antibody prepared against smooth muscle gelsolin was used to detect the presence of gelsolin in human lung fibroblast MRC-5 cells permeabilized with Triton X-100 (MRC-5 cell models). These cells contracted in the presence of MgATP and Ca2+ in doses over 1 microM. Immunofluorescence microscopy using phalloidin and antigelsolin antibody showed that gelsolin was distributed along the stress fibers, except for a marginal bundle of cells, when MRC-5 cells were growth-arrested in serum-depleted medium. Making use of immunoblotting and indirect immunofluorescence techniques, we demonstrated that gelsolin is not retained in the MRC-5 cell models. We used purified smooth muscle gelsolin as a specific agent to sever the actin filaments. Preincubation of MRC-5 cell models with gelsolin led to a destruction of stress fibers, in a dose- and Ca2+ -dependent manner. The contractility was also lost, in the same manner described above, thereby indicating that a continuous distribution of actin filaments within the stress fibers is required for cell contraction. Treatment of MRC-5 cells with the Ca2+ ionophore A23187 induced an extracellular Ca2+ -dependent contraction but not a massive destruction of stress fibers, thereby indicating that most of the endogenous gelsolin was inactive under these conditions. Our interpretation of these results is that increases in cytoplasmic Ca2+ concentrations are sufficient for the contraction but may be too transient to activate endogenous gelsolin and thereby disrupt the stress fibers. Indeed, the inhibition of contraction of the MRC-5 cell, as induced by smooth muscle gelsolin, required preincubation in the presence of Ca2+, before the addition of MgATP. These results suggest that destruction of the stress fibers by endogenous gelsolin, which leads to inhibition of cell contraction, may occur if the cytoplasmic Ca2+ is maintained at high concentrations for a few minutes.

Animals↗
PubMed1980

Myosin phosphorylation during contraction and relaxation of tracheal smooth muscle.

The role of myosin phosphorylation in regulating smooth muscle contraction has been investigated by quantitating the myosin phosphate content of tracheal smooth muscle frozen during contraction or relaxation. Myosin was purified from quick-frozen muscle samples with the aid of antibodies prepared against tracheal smooth muscle myosin, and the phosphate content was determined after separation of nonphosphorylated and phosphorylated myosin subunits by isoelectric focusing. The myosin phosphate content increased from an initial value of 0.50 to 1.1 mol of phosphate/mol of myosin within 3 min after the addition of 100 microM methacholine to resting tracheal smooth muscle. Myosin phosphorylation coincided temporally with the increase in isometric tension. Tracheal smooth muscles relaxed and the phosphate content decreased from 1.2 to 0.50 mol of phosphate/mol of myosin upon the addition of 10 microM atropine to muscles which had been previously contracted with 100 microM methacholine. Incubating methacholine-contracted muscles in a calcium-free Krebs buffer relaxed tracheal smooth muscles and reduced the phosphate content to 0.2 mol of phosphate/mol of myosin. Addition of 3 mM CaCl2 to these muscles elicited an increase in isometric tension concomitant with phosphorylation of myosin. These results support the hypothesis that myosin phosphorylation is important in regulating smooth muscle contraction.

Animals↗
PubMed1994

Effect of SR 47436, a novel angiotensin II AT1 receptor antagonist, on human vascular smooth muscle cells in vitro.

Proliferation of smooth muscle cells within the intima plays a key role in vascular occlusive disorders such as atherosclerosis and restenosis following balloon angioplasty. Among the factors that may be important in the development of vascular lesions, several authors have reported that the local angiotensin system participates in modulating the proliferation of smooth muscle cells after arterial injury. This study was therefore designed to characterize the antagonistic properties and to investigate the antiproliferative effect of a newly developed non-peptide angiotensin II AT1 receptor antagonist, SR 47436. This compound is a potent and competitive antagonist of the binding of [125I]angiotensin II to its receptor on cultured human aortic smooth muscle cells, exhibiting an IC50 value of 1.7 +/- 0.6 nM. SR 47436 was 10-fold more potent than DuP 753 (Losartan) (IC50 = 20.8 +/- 3.7 nM). In these same cells, SR 47436 potently inhibited the angiotensin II-induced [Ca2+]i increase (IC50 = 0.53 +/- 0.13 vs. 7.4 +/- 1.3 nM for DuP 753). Angiotensin II is a potent mitogen for human aortic smooth muscle cells in culture, exhibiting a maximum proliferative response at 1 microM. SR 47436 and Losartan prevented angiotensin II-induced proliferation of these cells in a dose-dependent manner (IC50 = 0.32 +/- 0.09 and 0.71 +/- 0.08 microM, respectively). SR 47436 displayed a marked in vitro inhibition of serum-induced smooth muscle cell proliferation (IC50 = 5.5 +/- 0.8 microM). A selective AT2 receptor antagonist, PD 123177 did not affect angiotensin II-induced responses in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Dystrophin does not influence regular cytoskeletal architecture but is required for contractile performance in smooth muscle aortic cells.

Cultured vascular smooth muscle cells express distinct histological phenotypes due to a contractile to synthetic stage transition. In this study, we compared the behaviour of cultured aortic smooth muscle cells from young normal and mdx mice. Morphological, immunobiochemical, immunocytochemical analyses and contraction studies of these cells demonstrated that (i) the cell cytoskeleton in mdx mice is not affected by the absence of dystrophin since proteins such as caldesmon, a-actin, and vinculin are expressed similarly in normal mice, (ii) utrophin (or dystrophin-related protein) overexpression does not compensate for the physiological and functional role of the lacking dystrophin. These data suggested that dystrophin and utrophin cannot substitute one another and may play different or complementary roles within smooth muscle cells.

Animals↗
PubMed2002

The sarcoplasmic reticulum and smooth muscle function: evidence from transgenic mice.

Smooth muscle Ca2+ handling is of major importance to understanding its function. A new approach utilizes molecular biology to develop transgenic mouse models in which the protein constituents of the various Ca2+ regulatory subsystems have been altered. Gene-targeted or gene-ablated (knockout) mice have been reported for the sarcoplasmic reticulum (SR) Ca2+ pump isoforms SERCA2, SERCA2a and SERCA3, the plasma membrane Ca2+ pump isoforms, PMCA1, PMCA2 and PMCA4, and the SR-associated protein, phospholamban (PLB), an inhibitor of SERCA2. A mouse line carrying a transgene for the smooth muscle specific expression of PLB has been reported. Evidence from studies using these mice combined with the classical pharmacological approaches has provided new insight into the relative role of the SR. We review this field with particular emphasis on PLB, since its modulation of SR function and smooth muscle contractility has the largest database. PLB via modulation of SERCA can play a major role in regulation of both phasic and tonic smooth muscle contractility. The use of transgenic mice has yielded surprises ,uch as PLB modulation of endothelial cell Ca2+ homeostasis, and the demonstration that PLB is the major site for A-kinase-mediated relaxation of mouse bladder. The use of these gene-altered models has provided evidence clearly implicating a major role for the SR in modulating smooth muscle Ca2+ and contractility, with the caveat that this modulation is tissue specific.

Animals↗
PubMedDate not supplied

The effects of L-ascorbic acid and prostaglandins on isolated tracheal smooth muscle.

On the isolated tracheal smooth muscle, L-ascorbic acid alone induced a dose-related relaxation. When L-ascorbic acid was added in a standard concentration of 10(-5) g/ml to increasing concentrations of PGE2, an increase of relaxation was evident. The opposite effect was observed when PGF2 alpha was added in presence of L-ascorbic acid: a depression of tracheal smooth muscle contraction occurred. L-ascorbic acid increased the relaxing effect of isoprenaline on the tracheal smooth muscle. The relaxation effect of L-ascorbic acid was abolished by propranolol. These data support the hypothesis, that the effect of L-ascorbic acid may be related to stimulation of beta adrenergic receptors.

Animals↗
PubMed1985

Immunohistochemical localization of smooth muscle myosin in normal human tissues.

Immunohistochemical localization of smooth muscle myosin, an immunologically distinct contractile protein, was achieved using rabbit anti-human uterine smooth muscle myosin antibodies. In immunodiffusion studies and in cryostat sections, these antibodies were highly specific and reacted with smooth muscle myosin but not with platelet, skeletal muscle, or cardiac muscle myosin. To evaluate comprehensively the structural profile of smooth muscle elements in normal human tissues, an indirect immunoperoxidase technique (peroxidase-antiperoxidase) was applied to a wide variety of specimens. Parallel studies comparing cryostat sections with fixed (10% formalin, B5, Bouin's, or Zenker's solution) paraffin-embedded tissues revealed optimal immunoreactivity, sensitivity, and specificity of staining for smooth muscle myosin using frozen tissues. Strong immunoreactivity was present in muscular tissues such as blood vessels and the muscularis of gastrointestinal and genitourinary tracts. Distinct delineation of smooth muscle elements, including individual smooth muscle cells, and their specific patterns of alignment and organization, were observed, e.g., cells comprising the muscularis mucosae and extending into the lamina propria of the gastrointestinal tract, and myoepithelial cells of skin, exocrine glands, and breast. This method provides excellent morphologic preservation and readily permits unambiguous identification of individual cells containing smooth muscle myosin.

Adult↗
PubMed1981

Protein phosphorylation in cardiac and vascular smooth muscle.

In the heart and arterial smooth muscles, several proteins are phosphorylated. This review summarizes our current knowledge about these phosphoproteins and their possible role in the function of these muscles. In the contractile apparatus, the phosphorylation of myosin light chain seems to be an integral part of the contraction cycle of arterial smooth muscle. However, in the heart the relationship between light chain phosphorylation-dehosphorylation and systolic-diastolic states remains open. In the heart, the phosphorylation of the inhibitory subunit of troponin, a myofibrillar protein, parallels the positive inotropic response induced by beta-adrenergic agonists. It seems likely that this phosphorylation is involved in the physiological stimulation of the heart by epinephrine. Cardiac sarcoplasmic reticulum contains a low-molecular-weight protein, phospholamban, the phosphorylation of which is required for Ca2+ transport. Ion fluxes through the heart sarcolemma may also be controlled through membrane protein phosphorylation. Key enzymes of the energy-yielding pathways in the heart, the pyruvate dehydrogenase multienzyme complex and phosphorylase, are turned on and off by phosphorylation-dephosphorylation mechanisms. Our understanding of protein phosphorylation in the heart has advanced greatly. In contrast, with the exception of the myosin light chain, much less is known about the many proteins phosphorylated in arterial smooth muscle.

Animals↗
PubMed1993

Can lipoprotein lipase be the culprit in cholesteryl ester accretion in smooth muscle cells in atheroma?

Bovine aortic smooth muscle cells and human skin fibroblasts were incubated with beta-very low density lipoprotein (beta VLDL) isolated from cholesterol-fed rabbits and labeled with [3H]cholesteryl oleate. Addition of lipoprotein lipase resulted in a 3.2-4.8-fold increase in cell associated radioactivity of which 45-61% was in free cholesterol, i.e., derived after intracellular hydrolysis. After exposure of smooth muscle cells to beta VLDL for up to 9 days and 60 min sodium heparin wash at 4 degrees C to remove extracellular surface bound lipoprotein, cellular cholesterol increase was 2 micrograms in controls and in the presence of lipoprotein lipase (LPL) it was tenfold higher. Addition of [3H]cholesteryl ester labeled beta VLDL during the last 48 h of incubation showed that 30-40% of total cellular label was in free cholesterol. This value represents the minimal cellular uptake of the added lipoprotein cholesteryl ester. Addition of recombinant apolipoprotein (apo) E to smooth muscle cells incubated with beta VLDL and [3H]oleate induced no further increase in [3H]cholesteryl oleate. We propose that following LPL-mediated binding of beta VLDL to heparan sulphate, this complex either undergoes endocytosis, or translocation of cholesteryl ester into the smooth muscle cells (SMC) occurs without endocytosis of the entire particle. The present results indicate that in the aortic wall macrophage-derived lipoprotein lipase could play a role in cholesteryl ester accretion in smooth muscle cells during atherogenesis.

Animals↗
PubMed2004

Suppression of WEE1 and stimulation of CDC25A correlates with endothelin-dependent proliferation of rat aortic smooth muscle cells.

Proliferation of vascular smooth muscle cells plays a key role in the pathogenesis of several disorders of the vascular wall. Endothelin (ET), a vasoactive peptide that signals through a G protein-coupled receptor, has been linked to mitogenesis in vascular smooth muscle cells, but the mechanistic details underlying this activity remain incompletely understood. In the present study, we demonstrate that ET-dependent mitogenesis in rat neonatal and adult aortic smooth muscle (RASM) cells is accompanied by an increase (up to 10-fold) in CDK2 activity, but not CDK2 protein levels. This effect is blocked almost entirely by PD98059 and UO126, implying involvement of the MEK/ERK signal transduction cascade in the activation. Extracts of ET-treated cells phosphorylate the N terminus of WEE1, an inhibitory kinase, which negatively regulates CDK2 activity through phosphorylation at Tyr(15), leading to a decrease in WEE1 activity and a reduction in levels of phospho-Tyr(15) in the CDK2 protein. ET also increases expression and activity of CDC25A, the regulatory phosphatase responsible for dephosphorylating Tyr(15). All of these effects are reversible following treatment with the MEK inhibitor PD98059. ET also increases levels of CDC2 activity in these cells in association with a decrease in levels of phospho-Tyr(15) on the CDC2 molecule. Phosphorylation of WEE1 is linked to ERK while phosphorylation of MYT1 (CDC2-selective inhibitory kinase) is tied to the ribosomal S6 kinase (RSK). In summary, ET controls progression through the cell cycle, in part, by increasing CDK2 and CDC2 activity through the MEK/ERK/RSK signal transduction pathway(s). This results from the phosphorylation and subsequent inactivation of two inhibitory kinases (WEE1 and MYT1) that tonically suppress CDK2 and CDC2 activity and activation of a phosphatase (CDC25A) that increases CDK2 activity.

Animals↗
PubMed1992

Direct inhibitory effect of calcitonin gene-related peptide and atrial natriuretic peptide on gastric smooth muscle cells via different mechanisms.

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to determine whether calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2', 5'-dideoxyadenosine, an inhibitor of adenylate cyclase, on the CGRP-induced or ANP-induced relaxation of gastric smooth muscle cells were examined. CGRP and ANP inhibited the contractile response produced by carbachol in a dose-dependent manner, and the values of IC50 were 3 nM and 2 nM, respectively. 2',5'-dideoxyadenosine significantly inhibited the relaxation produced by CGRP. On the other hand, 2',5'-dideoxyadenosine did not have any significant effect on the relaxation produced by ANP. These results demonstrate the difference between intracellular mechanism responsible for gastric smooth muscle relaxation by CGRP and the mechanism responsible for muscle relaxation by ANP, and strongly suggest that the action of CGRP is mediated by adenosine 3',5'-cyclic monophosphate.

Animals↗
PubMed1986

Methacholine sensitivity and cAMP protein kinase in tracheal smooth muscle.

We studied regional variation in canine trachealis smooth muscle sensitivity and responsiveness to methacholine as well as basal and methacholine-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-dependent protein kinase activity. The trachea between the cricoid cartilage and the carina was divided into three segments of equal length (designated cervical, middle, and thoracic regions), each consisting of approximately 12-14 cartilage rings. Smooth muscle strips from each of the three regions were exposed to cumulative half-log increments of methacholine chloride. The sensitivity (-log EC50) and responsiveness (force per cross-sectional area and force per milligram protein) of the smooth muscle to methacholine in each region was determined from these data. Smooth muscle strips from cervical and thoracic regions were frozen before and after exposure to cumulative half-log increments of methacholine up to each region's previously determined EC50. Frozen samples were assayed for cAMP content or cAMP-dependent protein kinase activity. The relationship between resting tension and methacholine sensitivity and responsiveness were studied. For the size strips we used, 4 g resting tension set the average cervical and thoracic strips at 96 and 101% of their optimal length, respectively. The methacholine EC50 was not affected by a variation in resting tension. Sensitivity to methacholine was 7.1, 6.8, and 6.5 for cervical, middle, and thoracic regions, respectively. The responsiveness of the cervical and thoracic smooth muscle to methacholine was 16.4 and 16.3 g force/mm2, respectively, at an EC50 methacholine. Basal cAMP was lower in cervical smooth muscle than in thoracic. cAMP-dependent protein kinase activity ratios under both basal and EC50 methacholine-stimulated conditions were lower in cervical smooth muscle than in thoracic. We have observed in trachealis smooth muscle an inverse relationship between methacholine sensitivity and either cAMP or cAMP-dependent protein kinase activity. We suggest that cAMP and cAMP-dependent protein kinase play a role in the regulation of airway smooth muscle sensitivity to cholinergic agonists.

Animals↗