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.

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.

239 USE OF CYCLIC ADENOSINE MONOPHOSPHATE MODULATORS IN IN VITRO PRODUCTION OF BOVINE EMBRYOS

2015 ◽  
Vol 27 (1) ◽  
pp. 209
Author(s):  
T. Fanti ◽  
N. M. Ortega ◽  
R. Garaguso ◽  
M. J. Franco ◽  
C. Herrera ◽  
...  
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Basal Medium ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Control Group ◽  
Hatching Rate ◽  
Bovine Embryos ◽  
Oocyte Competence

In vitro embryo production systems (IVP) try to emulate and enhance molecular events that occur in in vivo reproductive systems in order to increase, not only the number of embryos generated, but also their quality. Despite advances, IVP processes are still inefficient compared with in vivo systems. Several studies have attributed this deficiency to a lack of oocyte competence due to spontaneous premature resumption of meiotic maturation in the oocyte following the removal from its follicular environment. Therefore, our objective was to increase oocyte competence avoiding premature resumption of meiosis by using cyclic adenosine monophosphate modulators. Cumulus-oocyte complexes (COC) were obtained from ovaries of slaughterhouses, washed, and randomly allocated in 2 culture systems. Oocytes in the control group (IVM) were cultured for a period of 24 h in basal medium TCM-199 with EGF (1 µg mL–1) supplemented with rhFSH (25 mIU mL–1). Oocytes in the biphasic in vitro maturation (b-IVM) group were cultured for 2 h in a basal medium supplemented with a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 500 µM), and an activator of adenylate cyclase (forskolin, 100 µM). Subsequently, COC were washed and cultured in basal medium supplemented with cilostamide (20 µM) and rhFSH (25 mIU mL–1) for 24 h. Maturation rates were analysed and IVF was performed with a dose of 1 × 106 sperm cells mL–1 in IVF-SOF medium. The presumptive zygotes were cultured in continuous-single-culture medium (Irvine) supplemented with 8 mg mL–1 of BSA until they reached the blastocyst stage. No significant differences in maturation, cleavage, and cryotolerance were observed between b-IVM and IVM groups (P > 0.05; Table 1). This study showed that b-IVM produced a significant increase in IVP compared with the control (IVM) at Days 7 and 8 (P < 0.01). Blastocyst hatching rate was significant (P < 0.05) for both treatment and day of analysis. The b-IVM group yielded an increase of 10 and 7.5% at Days 7 and 8, respectively, of IVP. The biphasic maturation showed an improvement in quality regarding the control group, in the timing analysis of production, and hatching percentages, and these results show that the use of cyclic adenosine monophosphate modulators in the oocyte maturation process enhances oocyte competence, which is reflected in increased productivity and embryo quality. We propose this treatment as an alternative to the standard protocols currently used in IVP of bovine embryos. Table 1.Effect of treatment on maturation, cleavage, and cryotolerance

scholarly journals EVALUATION OF IN-VITRO VASORELAXANT EFFECT (POTENTIAL ANTIHYPERTENSIVE) OF KIGELIA AFRICANA FRUIT METHANOL EXTRACT ON POTASSIUM CHLORIDE AND PHENYLEPHRINE INDUCED TENSION IN WISTAR RAT AORTA

2020 ◽  
Vol 4 (3) ◽  
pp. 470-475
Author(s):  
A. O. Isah ◽  
M. Idu ◽  
A. A. Abdulrahman ◽  
F. Amaechina
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Potassium Chloride ◽  
Methanol Extract ◽  
Muscle Relaxation ◽  
Rat Aorta ◽  
Smooth Muscle Relaxation ◽  
Organ Bath ◽  
Vasorelaxant Effect

This research on Kigelia africana was conducted in order to ascertain its ability to relax excited vascular smooth muscle in rat aorta. Preliminary investigation on whether the plant exhibits antihypertensive property was done before the evaluation of in vitro vasorelaxant effect. The vasorelaxant activity was determined using in vitro method on rat aorta with the aid of perfusion apparatus with a detachable organ bath. The administration of potassium chloride (KCl) raised the tension from 1.0 to 1.31 indicating that the aorta got to its peak of contraction. At 10 and 20mg/kg, the tension dropped significantly, showing relaxation of the smooth muscle while at 5mg/kg, drop in tension was insignificant at p˂0.05. However, at some of the doses, towards the end of experiment, there was steady resurge in tension showing that the aorta resumed contraction. On the application of phenylephrine (PE), the tension rose to 1.18g. On administration of the extract, the tension dropped slightly showing mild vascular smooth muscle relaxation. From the results obtained, there was seeming similarity in the action of the K. africana compared to amlodipine/Ramipril in KCl and PE induced tension in aorta respectively. However, at 10 and 20mg/kg, a substantial decrease in tension was noted indicating that the extract action is dose dependent. Thus, from this in-vitro smooth muscle relaxation study in rats, the methanol extract of K. africana has depressant property that was likely expressed by enhancing the closing of voltage operated calcium channel and ACE inhibiting activity in KCl and Phenylephrine induced tension respectively.

scholarly journals Effects of Aqueous Extract of Curcuma Longa Rhizome On Motility of Isolated Rabbit Jejunum

2019 ◽  
Vol 2 (1) ◽  
pp. 13-22
Author(s):  
B Umaru
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Aqueous Extract ◽  
Curcuma Longa ◽  
Muscle Relaxation ◽  
Soxhlet Extraction ◽  
Smooth Muscle Contraction ◽  
Smooth Muscle Relaxation ◽  
Rabbit Jejunum

Turmeric (curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family and the order Zingerberales. It is widely cultivated and used in the treatment of various ailments. In this study, the effect of aqueous extract of C. longa on isolated rabbit jejunum was investigated in vitro using Physiograph (Meditech, India). The rhizome of Curcumin was extracted using Soxhlet extraction method and distilled water was used as a solvent. The elemental analysis was determined using AAS and the result revealed the presence of Potassium, Magnesium, Iron and Nitrogen. The percentage concentrations of trace elements in the aqueous Curcumin rhizome were within the WHO standard limit. The aqueous extract at concentration tested (100 mg/ml) significantly decreased (p<0.05) jejunum smooth muscle contraction. Addition of Atropine (1mM) or Propranolol (1mM) further decreased the amplitude of jejunum smooth muscle contraction. Curcumin rhizome (100 mg/ml) blocked contraction induced by Ach (0.001μg/ml). The result of this work has shown that rhizome of C. longa produced jejunum smooth muscle relaxation, plant extract with antispasmodic activity may reduce gastrointestinal motility thereby delay gastric emptying and may be important in treatment of disease ailments like diarrhoea and colic.

258 IMPACT OF MILRINONE AND FORSKOLIN ON THE EFFICIENCY AND QUALITY OF BOVINE OOCYTE IN VITRO MATURATION

2013 ◽  
Vol 25 (1) ◽  
pp. 277
Author(s):  
E. Stachowiak ◽  
K. Papis ◽  
J. Karasiewicz ◽  
J. A. Modlinski
Keyword(s):  
In Vitro Maturation ◽  
Combined Treatment ◽  
Phosphodiesterase Inhibitor ◽  
Microscopic Analysis ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Experimental Conditions ◽  
Oocyte Meiosis

The efficiency of in vitro maturation (IVM) of bovine oocytes remains inferior compared with maturation in vivo. Recently, some modifications of in vitro maturation (IVM) procedures have been proposed, such as simulated physiological maturation (Gilchrist 2011 Reprod. Fertil. Dev. 23, 23–31). In our experiment, a comparison of the traditional IVM efficiency with maturation after oocyte meiosis inhibition using roscovitine or with a modified two-step maturation using forskolin (cyclic adenosine monophosphate stimulator) and milrinone (type-3 phosphodiesterase inhibitor) was performed. Control oocytes obtained from slaughterhouse-derived ovaries were subjected to the traditional 24-h maturation in TCM-199 medium supplemented with sodium pyruvate, l-glutamine, gentamicin, 10% FCS, and hormones (pregnant mare’s serum gonadotropin and hCG, PG 600, Intervet, Kenilworth, NJ, USA). The roscovitine (50 µM, 24 h) inhibitory treatment was accomplished in the same medium (without hormones) and subsequently, traditional 24-h IVM was performed. The same TCM-199 medium (with hormones) supplemented with forskolin (100 µM) and milrinone (50 µM) was used for the first step (17 h) of the two-step maturation, whereas the second step (7 h) was performed in the same TCM-199 medium devoid of forskolin and milrinone. Fertilization with frozen sperm processed using TALP media was performed in TALP supplemented with heparin, penicillamine, hypotaurine, epinephrine, and BSA. In vitro culture of presumptive zygotes was performed in CR1aa medium. Portions of oocytes from all treatments after maturation and after fertilization procedures were stained and subjected to microscopic analysis. There were no differences in terms of maturation and fertilization rates between treatments. However, roscovitine-mediated inhibition of maturation performed in our experimental conditions was efficient and reversible, but harmful for subsequent embryo development. On the other hand, two-step maturation was equally as efficient as (but not better than) traditional IVM in all aspects examined in the present study (Table 1). In conclusion, the forskolin and milrinone combined treatment during the IVM procedure gives hope for fully efficient IVM. However, to achieve this goal, more research is necessary. Table 1.Development of embryos after different oocyte maturation procedures1

Differential effects of nitrovasodilators and nitric oxide on porcine tracheal and bronchial muscle in vitro

1994 ◽  
Vol 77 (3) ◽  
pp. 1142-1147 ◽  
Author(s):  
K. Stuart-Smith ◽  
T. C. Bynoe ◽  
K. S. Lindeman ◽  
C. A. Hirshman
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Ringer Solution ◽  
Smooth Muscle Relaxation ◽  
Response Curves

Nitrovasodilators and nitric oxide relax airway smooth muscle. The mechanism by which nitrovasodilators are thought to act is by release of nitric oxide, but the importance of nitric oxide in nitrovasodilator-induced airway smooth muscle relaxation is unclear. The aim of this study was to compare the relaxing effects of nitric oxide itself with those of nitrovasodilators in porcine tracheal muscle and intrapulmonary airways and to investigate the mechanisms involved. Strips of porcine tracheal smooth muscle, rings of bronchi, and strips of bronchi from the same animal were suspended in organ chambers in modified Krebs Ringer solution (95% O2–5% CO2, 37 degrees C). Tissues were contracted with carbachol, and concentration-response curves to nitric oxide, sodium nitroprusside, and SIN-1 (an active metabolite of molsidomine) were obtained. All tissues relaxed to sodium nitroprusside, SIN-1, and nitric oxide. The relaxation to nitric oxide but not to SIN-1 or sodium nitroprusside was inhibited by methylene blue. Tissues pretreated with methylene blue that failed to relax to nitric oxide were, however, relaxed by sodium nitroprusside. These results demonstrate that nitrovasodilators relax airways by a mechanism other than by or in addition to the release of nitric oxide.

l-Glutamine in vitro regulates rat aortic glutamate content and modulates nitric oxide formation and contractility responses

2007 ◽  
Vol 293 (1) ◽  
pp. C142-C151 ◽  
Author(s):  
David Schachter
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Plasma Concentrations ◽  
Smooth Muscle Relaxation ◽  
No Formation ◽  
Ketoacid Dehydrogenase ◽  
Glutamate Synthesis

These studies test the hypothesis that l-glutamine at its physiological plasma concentration, ∼0.5 mM, can increase tissue content and net synthesis of glutamate in rat aortic segments in vitro, thereby mediating relaxation of the underlying smooth muscle in the elastic reservoir region of the thoracic aorta. Aortic segments were incubated in an isotonic medium with and without 21 amino acids at their normal plasma concentrations. Of these amino acids only l-glutamine and l-leucine at their plasma concentrations increased glutamate synthesis and content. Tissue glutamate content resulting from increasing concentrations of each precursor reached an upper level of ∼1.3–1.6 μmol/g wet wt. Regulation of the tissue glutamate content involves an interaction of the synthetic pathways in which l-glutamine inhibits the endothelial leucine-to-glutamate pathway. l-Glutamine increases nitric oxide (NO) formation, and NO inhibits the controlling enzyme of the endothelial leucine-to-glutamate pathway, the branched-chain α-ketoacid dehydrogenase complex. Treatment of precontracted aortic rings with 0.5 mM l-glutamine elicits smooth muscle relaxation, a response that requires endothelial nitric oxide synthase activity and an intact endothelium. The results demonstrate that in vitro l-glutamine at its normal concentration in plasma can regulate rat aortic glutamate content and modulate NO formation and contractility responses of the thoracic aortic wall.

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