scholarly journals Impact of a Newly Synthesized Molecule (2-chloro-N-(1-(3,4-dimethoxyphenyl) propan-2-yl)-2-phenylacetamide) on the Bioelectrogenesis and the Contractile Activity of Isolated Smooth Muscles

Folia Medica ◽  
2020 ◽  
Vol 62 (3) ◽  
pp. 532-538
Author(s):  
Vera N. Gledacheva ◽  
Iliyana D. Stefanova ◽  
Valeri I. Slavchev ◽  
Rayna G. Ardasheva ◽  
Atanas D. Kristev ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Mechanical Activity ◽  
Aziridine Ring ◽  
Male Wistar Rats ◽  
Dependent Signal ◽  
Sucrose Gap ◽  
Relaxing Effect ◽  
Ca2 Channels

Introduction: Examination of the potential possibilities of 2-chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide (IQP) to affect bioelectrogenesis and the contractile activity of isolated smooth muscles (SM) from stomach. Aim: Having in mind the structural similarities between the molecules of papaverine and IQP, the aim of the present study was to examine such features of the newly synthesized molecule that may potentially affect the muscle tonus, spontaneous bioelectrical and contractile activities of smooth muscles isolated from the stomach, basing on specific mechanisms of papaverine. Materials and methods: The synthesis of IQP is based on the initially formed aziridine ring by principles of Gilbert’s reaction. Impact of IQP on the bioelectrogenesis and the contractile activity of isolated smooth muscles from male Wistar rats was measured by the single sucrose-gap method and isometrically recorded. Results: IQP (1×10-5 – 2.5×10-4 mol/l) causes muscle relaxation, producing changes in two processes that have influence on the mechanical activity of smooth muscles:1.    Blocked Ca2+ influx through the potential-dependent membrane Ca2+ channels, followed in turn by lowering the Ca2+ intracellular levels. This effect is proved by the changes in the frequency and amplitude of spike-potentials in sucrose-bridge experiments when IQP is applied.2.    Activation of a cAMP-dependent signal cascade. The relaxing effect of IQP was significantly reduced in the presence of KT5720(5×10-6 mol/l), an inhibitor of protein kinase A. Conclusion: We assume that there might be interconnections between these two IQP-dependent processes, because PKA-dependent phosphorylation of the L-type Ca2+ channels in smooth muscles provokes a reaction of inactivation.

Outward current and repolarization in hypoxic rat myocardium

1983 ◽  
Vol 244 (3) ◽  
pp. H341-H350
Author(s):  
C. H. Conrad ◽  
R. G. Mark ◽  
O. H. Bing
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Iodoacetic Acid ◽  
Mechanical Activity ◽  
Potential Range ◽  
Papillary Muscles ◽  
Rat Myocardium ◽  
Cable Properties ◽  
Sucrose Gap

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.

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.

Effects of ischemia and myogenic activity on active and passive mechanical properties of rat cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2268-H2275 ◽  
Author(s):  
Rebecca J. Coulson ◽  
Naomi C. Chesler ◽  
Lisa Vitullo ◽  
Marilyn J. Cipolla
Keyword(s):  
Contractile Activity ◽  
Cerebral Arteries ◽  
Biomechanical Properties ◽  
Short Term ◽  
Mechanical Stiffness ◽  
Middle Cerebral Arteries ◽  
Male Wistar Rats ◽  
Myogenic Activity ◽  
Activity Dependent

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.

scholarly journals Identification of serotonergic (5HT1A-type) receptors in broiler small intestine by application of serotonin and its agonists and antagonists

2011 ◽  
Vol 65 (1-2) ◽  
pp. 51-59 ◽  
Author(s):  
Indira Mujezinovic ◽  
Vitomir Cupic ◽  
Ahmed Smajlovic ◽  
Mehmed Muminovic
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Smooth Muscles ◽  
Muscle Layer ◽  
Force Transducer ◽  
Mechanical Activity ◽  
Organ Bath ◽  
Pathological Conditions ◽  
Isolated Organ Bath ◽  
Longitudinal Layer

Serotonin or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter synthesised from L-tryptophan in serotonergic neurons and enterochromaffin cells of the gastrointestinal tract. This neurotransmitter is widely distributed in the animal and plant kingdom and regulates some central and peripheral functions through several types of specific serotonergic (5-HT) receptors. Since it is known that the effect of serotonin, especially in pathological conditions, is very important, we believe that determining the types of receptors for this substance would make it possible to use their agonist or antagonists, which would undoubtedly enhance the pharmacotherapy of functional disruption of the small intestine in broilers. Investigations were carried out on isolated smooth muscle strips of the circular and longitudinal layer of the broiler small intestine (strip dimension 3-4 mm x 2 cm). The muscle strips were placed in an isolated organ bath. The mechanical activity of the preparations was recorded via an isotonic force transducer coupled to a pen recorder. This was done following the addition of serotonin (nonselective 5-HT agonist), 8-OH-DPAT (selective 5-HT1A agonist) and spiroxatrin (selective 5-HT1A antagonist). The sensitivity of the tissues to acetylcholine was tested before starting the experiments. Using the obtained results, it can be concluded that 5HT1A type receptors are present in smooth muscles of the broiler small intestine, duodenum and ileum, especially in the longitudinal smooth muscle layer which reacted with contractions even to low serotonin concentration (10-6), but not in the jejunum.

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.

scholarly journals Electrophysiology of Syncytial Smooth Muscle

2019 ◽  
Vol 13 ◽  
pp. 117906951882191 ◽  
Author(s):  
Rohit Manchanda ◽  
Shailesh Appukuttan ◽  
Mithun Padmakumar
Keyword(s):  
Smooth Muscle ◽  
Action Potentials ◽  
Signal Analysis ◽  
Computational Models ◽  
Vas Deferens ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Biophysical Analysis ◽  
Recent Developments ◽  
The Many

As in other excitable tissues, two classes of electrical signals are of fundamental importance to the functioning of smooth muscles: junction potentials, which arise from neurotransmission and represent the initiation of excitation (or in some instances inhibition) of the tissue, and spikes or action potentials, which represent the accomplishment of excitation and lead on to contractile activity. Unlike the case in skeletal muscle and in neurons, junction potentials and spikes in smooth muscle have been poorly understood in relation to the electrical properties of the tissue and in terms of their spatiotemporal spread within it. This owes principally to the experimental difficulties involved in making precise electrical recordings from smooth muscles and also to two inherent features of this class of muscle, ie, the syncytial organization of its cells and the distributed innervation they receive, which renders their biophysical analysis problematic. In this review, we outline the development of hypotheses and knowledge on junction potentials and spikes in syncytial smooth muscle, showing how our concepts have frequently undergone radical changes and how recent developments hold promise in unraveling some of the many puzzles that remain. We focus especially on computational models and signal analysis approaches. We take as illustrative examples the smooth muscles of two organs with distinct functional characteristics, the vas deferens and urinary bladder, while also touching on features of electrical functioning in the smooth muscles of other organs.

Endogenous prostaglandin in guinea pig taenia coli

1976 ◽  
Vol 230 (1) ◽  
pp. 149-157 ◽  
Author(s):  
T Yamaguchi ◽  
B Hitzig ◽  
RF Coburn
Keyword(s):  
Guinea Pig ◽  
Surface Membrane ◽  
Membrane Resistance ◽  
Threshold Concentration ◽  
Mechanical Activity ◽  
Taenia Coli ◽  
Endogenous Prostaglandin ◽  
Sucrose Gap ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Prostaglandin (PGE) is synthesized in the guinea pig taenia coli. A low threshold concentration for an effect of exogenous PGE1 or PGE2 on spontaneous mechanical activity was demonstrated. The PG synthetase inhibitors aspirin, indomethacin, and 5,8,11,14-eicosatetraynoic acid, at concentrations that inhibited PGE efflux, had effects on spontaneous mechanical activity, membrane potential, membrane resistance, and evoked and spontaneous action potentials (single and double sucrose-gap methods) that were consistent with an action due to inhibition of membrane PGE concentration. The threshold concentration of indomethacin, which inhibited PGE efflux, was the same as the concentration that inhibited spontaneous mechanical activity. Pretreatment with ouabain (10(-6)-10(-5) g/ml) or elevated extracellular K+ (29 and 126 mM) made the guinea pig taenia coli entirely refractory to exogenous PGE1 or PGE2; the mechanical effects of the three prostaglandin synthetase inhibitors also were absent in the presence of elevated K+ or ouabain. The data are consistent with a hypothesis that, under conditions of our experiments, endogenous PGE has an effect on resting tension and spontaneous mechanical activity and on properties of the surface membrane of the guinea pig taenia coli.

Contractile arrest accelerates myosin heavy chain degradation in neonatal rat heart cells

1992 ◽  
Vol 263 (3) ◽  
pp. C642-C652 ◽  
Author(s):  
A. M. Samarel ◽  
M. L. Spragia ◽  
V. Maloney ◽  
S. A. Kamal ◽  
G. L. Engelmann
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Contractile Activity ◽  
Neonatal Rat ◽  
Mechanical Activity ◽  
Mechanical Forces ◽  
Channel Blockade ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Mechanical forces influence the growth and metabolism of a variety of cells, including cultured neonatal rat ventricular myocytes. To determine whether mechanical activity affected the synthesis and turnover of myosin heavy chain (MHC) in these striated muscle cells, MHC fractional degradative rates were measured in spontaneously beating cells and in arrested myocytes in which contractile activity was prevented by L-channel blockade (with verapamil, nifedipine, nisoldipine, and diltiazem) or K+ depolarization. MHC degradative rates were measured as the difference between rates of MHC synthesis and accumulation and in pulse-chase biosynthetic labeling experiments. Both methods indicated that contractile arrest markedly increased MHC degradation. Contractile arrest produced by L-channel blockade accelerated MHC degradation to a greater extent than K+ depolarization. The signal transduction pathway linking contractile activity to alterations in MHC degradation did not involve protein kinase C (PKC), because MHC degradation was unaffected by activating PKC in arrested cells or inhibiting PKC in spontaneously beating cells. Chloroquine and E-64 did not suppress the accelerated MHC degradation, suggesting that the rate-limiting step in MHC turnover occurred before degradative processing by cellular proteinases. Using a computer simulation, we hypothesize that the rate-limiting step in MHC turnover preceded (or was coincident with) MHC release from thick filaments. Thus mechanical forces may influence MHC half-life by regulating the rate of myosin disassembly.

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