scholarly journals ANTIPHOSPHODIESTERASE ACTIVITY AND NONSPECIFIC SMOOTH MUSCLE RELAXATION TESTED ON INTESTINAL SMOOTH MUSCLES

1975 ◽  
Vol 25 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Nobuhiro INATOMI ◽  
Issei TAKAYANAGI ◽  
Keijiro TAKAGI
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Smooth Muscle Relaxation ◽  
Intestinal Smooth Muscles

Role of cGMP in relaxation of vascular and other smooth muscle

1989 ◽  
Vol 67 (4) ◽  
pp. 251-262 ◽  
Author(s):  
Kanji Nakatsu ◽  
Jack Diamond
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Phosphodiesterase Inhibitors ◽  
Current Evidence ◽  
Smooth Muscle Relaxation ◽  
Drug Induced ◽  
Intracellular Cgmp ◽  
Tissue Content

The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.Key words: cGMP, vascular relaxation, smooth muscle relaxation, vasodilators.

scholarly journals The effects of wild-type and mutant SOD1 on smooth muscle contraction

2015 ◽  
Vol 67 (1) ◽  
pp. 187-192 ◽  
Author(s):  
Aleksandra Nikolic-Kokic ◽  
Zorana Orescanin-Dusic ◽  
Ivan Spasojevic ◽  
Dusko Blagojevic ◽  
Zorica Stevic ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Smooth Muscle Relaxation ◽  
Transgenic Rat ◽  
Wild Type ◽  
Liver Copper ◽  
Ion Conducting ◽  
G93a Sod1

In this work we compared the mutated liver copper zinc-containing superoxide dismutase (SOD1) protein G93A of the transgenic rat model of familial amyotrophic lateral sclerosis (FALS), to wild-type (WT) rat SOD1. We examined their enzymatic activities and effects on isometric contractions of uteri of healthy virgin rats. G93A SOD1 showed a slightly higher activity than WT SOD1 and, in contrast to WT SOD1, G93A SOD1 did not induce smooth muscle relaxation. This result indicates that effects on smooth muscles are not related to SOD1 enzyme activity and suggest that heterodimers of G93A SOD1 form an ion-conducting pore that diminishes the relaxatory effects of SOD1. We propose that this type of pathogenic feedback affects neurons in FALS.

Roles of CaM kinase II and phospholamban in SNP-induced relaxation of murine gastric fundus smooth muscles

2006 ◽  
Vol 291 (2) ◽  
pp. C337-C347 ◽  
Author(s):  
Minkyung Kim ◽  
In Soo Han ◽  
Sang Don Koh ◽  
Brian A. Perrino
Keyword(s):  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Cyclopiazonic Acid ◽  
Gastric Fundus ◽  
Smooth Muscle Relaxation ◽  
Cam Kinase Ii ◽  
Cam Kinase ◽  
No Donor

The mechanisms by which nitric oxide (NO) relaxes smooth muscles are unclear. The NO donor sodium nitroprusside (SNP) has been reported to increase the Ca2+ release frequency (Ca2+ sparks) through ryanodine receptors (RyRs) and activate spontaneous transient outward currents (STOCs), resulting in smooth muscle relaxation. Our findings that caffeine relaxes and hyperpolarizes murine gastric fundus smooth muscles and increases phospholamban (PLB) phosphorylation by Ca2+/calmodulin (CaM)-dependent protein kinase II (CaM kinase II) suggest that PLB phosphorylation by CaM kinase II participates in smooth muscle relaxation by increasing sarcoplasmic reticulum (SR) Ca2+ uptake and the frequencies of SR Ca2+ release events and STOCs. Thus, in the present study, we investigated the roles of CaM kinase II and PLB in SNP-induced relaxation of murine gastric fundus smooth muscles. SNP hyperpolarized and relaxed gastric fundus circular smooth muscles and activated CaM kinase II. SNP-induced CaM kinase II activation was prevented by KN-93. Ryanodine, tetracaine, 2-aminoethoxydiphenylborate, and cyclopiazonic acid inhibited SNP-induced fundus smooth muscle relaxation and CaM kinase II activation. The Ca2+-activated K+ channel blockers iberiotoxin and apamin inhibited SNP-induced hyperpolarization and relaxation. The soluble guanylate cyclase inhibitor 1 H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one inhibited SNP-induced relaxation and CaM kinase II activation. The membrane-permeable cGMP analog 8-bromo-cGMP relaxed gastric fundus smooth muscles and activated CaM kinase II. SNP increased phosphorylation of PLB at Ser16 and Thr17. Thr17 phosphorylation of PLB was inhibited by cyclopiazonic acid and KN-93. Ser16 and Thr17 phosphorylation of PLB was sensitive to 1 H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one. These results demonstrate a novel pathway linking the NO-soluble guanylyl cyclase-cGMP pathway, SR Ca2+ release, PLB, and CaM kinase II to relaxation in gastric fundus smooth muscles.

Participation of cAMP in tacrine-induced gastric smooth muscle relaxation

2011 ◽  
Vol 6 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Natalia Prissadova ◽  
Mariana Argirova ◽  
Athanas Krastev ◽  
Valentin Turiiski ◽  
Rayna Ardasheva
Keyword(s):  
Smooth Muscle ◽  
Intracellular Signaling ◽  
Muscle Relaxation ◽  
Acetylcholinesterase Inhibitor ◽  
Smooth Muscles ◽  
Phosphodiesterase Inhibitor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Smooth Muscle Relaxation

AbstractTacrine, a well-known acetylcholinesterase inhibitor, applied in concentrations higher than 2×10−5 mol/l promoted Ca2+-independent relaxation of rat gastric smooth muscles in experiments in vitro. The relaxation was not cholinergic and was a result of influence of tacrine over intracellular signaling pathways regulating smooth muscle contraction/relaxation. The nature of this untypical muscle relaxation was studied by using smooth muscle strips isolated from rat stomach. Their bioelectrical and mechanical responses were recorded after treatment with tacrine and different activators or blockers of intracellular pathways involved in muscle contractility. Following the activation of adenylate cyclase with 1×10−6 mol/l forskolin and increase in the concentration of cyclic adenosine monophosphate (cAMP) after application of 4×10−5 mol/l SQ22536, a significant decrease in the muscle relaxation was observed. Theophylline (2×10−4 mol/l), a phosphodiesterase inhibitor, had no effect on the amplitude of tacrine-induced relaxation. The latter was also reduced by inhibition of protein kinase A (PKA) with 5×10−6 mol/l KT5720. These findings support the assumption that tacrine promoted smooth muscle relaxation through PKA-induced phosphorylation and inhibition of myosin light chain kinase activity. The reduction of spike-linked Ca2+ influx provoked by tacrine was probably a secondary contributing process, associated with an influence of increased cAMP level on Ca2+ channels.

scholarly journals A.122 Vascular effects of propofol: smooth muscle relaxation in human isolated veins and arteries

1996 ◽  
Vol 76 ◽  
pp. 38-39
Author(s):  
Eric Le Pelley ◽  
Pierre Corbi ◽  
Thierry Chataigneau ◽  
Robert Tricoche ◽  
Jacques Fusciardi
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Vascular Effects

216Acute administration of estradiol induces bladder smooth muscle relaxation through non-genomic pathways

2005 ◽  
Vol 4 (3) ◽  
pp. 56
Author(s):  
M. Dambros ◽  
P. Palma ◽  
C. Riccetto ◽  
R. Fraga ◽  
M. Thiel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Bladder Smooth Muscle

scholarly journals Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis

2003 ◽  
Vol 12 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Freek J. Zijlstra ◽  
Marieke E. van Meeteren ◽  
Ingrid M. Garrelds ◽  
Maarten A.C. Meijssen
Keyword(s):  
Smooth Muscle ◽  
Intestinal Permeability ◽  
Muscle Activation ◽  
Tap Water ◽  
Water Solution ◽  
Smooth Muscles ◽  
Distal Colon ◽  
Mucosal Inflammation ◽  
Smooth Muscle Relaxation ◽  
Organ Bath

Background:Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, anin vitroorgan bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth muscle contractility in different segments of the colon.Methods and materials:BALB/c mice were exposed to a 10% dextran sulphate sodium drinking water solution for 7 days to induce a mild colitis, while control mice received normal tap water. Intestinal segments were placed in an oxygenated organ bath containing Krebs buffer. Permeability was measured by the transport of the marker molecules3H-mannitol and14C-polyethyleneglycol 4000. Contractility was measured through a pressure sensor. Smooth muscle relaxation was obtained by salbutamol and l-phenylephrine, whereas contraction was achieved by carbachol and 1-(3-chlorophenyl)-biguanide.Results:The intensity of mucosal inflammation increased throughout the colon. Also, regional differences were observed in intestinal permeability. In both normal and inflamed distal colon segments, permeability was diminished compared with proximal colon segments and the non-inflamed ileum. Permeability in inflamed distal colon segments was significantly decreased compared with normal distal segments. Pharmacologically induced relaxation of smooth muscles did not affect this diminished permeability, although an increased motility positively affected permeability in inflamed and non-inflamed distal colon.Conclusions:Inflammation and permeability is inversely related. The use of pro-kinetics could counteract this disturbed permeability and, in turn, could regulate the disturbed production of inflammatory mediators.

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