Effect on muscle contractions

As cited in the section Perspectives for the Future, specific inhibitors or activators of channels, pumps, and transporters constitute the largest single class of drugs produced by the pharmaceutical Industry. Skeletal muscle contraction is caused by elevation of Ca concentration in the cytosol. What Is the expected effect on muscle contraction of selective drug Inhibition of sarcoplasmic reticulum (SR) P-class Ca ATPase ... 

Pedersen, T. H., O. B. Nielsen, G. D. Lamb, and D. G. Stephenson. Intracellular Acidosis Enhances the Excitability of Working Muscle. Soence305, 1144—1147 (2004). [Primary article on lactic acid and its effects on muscle contraction.]... 

In functional electrical stimulation, the typical stimulation waveform is a train of rectangular pulses. This shape is used because of its effectiveness as well as relative ease of generation. All three parameters of a stimulation train, that is, frequency, amplitude, and pulse-width, have effect on muscle contraction. Generally, the stimulation frequency is kept as low as possible, to prevent muscle fatigue and to conserve stimulation energy. The determining factor is the muscle fusion frequency at which a smooth muscle response is obtained. This frequency varies however, it can be as low as 12-14 Hz and as high as 50 Hz. In most cases, the stimulation frequency is kept constant for a certain application. This is true both for surface as well as implanted electrodes. 

The biological activity of the synthetic glycosylated substance P derivatives was studied by measuring their effects on muscle contraction of longitudinal... 

Katayama T (1957) Chemical studies on volatile constituents on seaweeds - Xn. Effect on muscle contraction of earthworms. Bull Jpn Soc Sci Fish 22 253-256... 

Although there are no positive Indications that structured water plays a role in the mechanism of muscle contraction, a theoretical mechanism employing the Ice lattice can be devised. Such a scheme uses protein-water interactions In two phases Involving Interchanging enol and keto forms of the peptide carbonyls, and was first mentioned as a possible contraction mechanism In an Informal discussion A coiq>lete elaboration of this concept as a model for muscle contraction has been publlshed. This model, which employs water In an active structural and mechanical sense, may be relevant to the earlier observation of Goodall that proton transfer could be the rate-determining step in muscle contraction. Home and Johnson have shown that variables such as pressure, ten erature, and Isotope (D2O) may Influence proton transfer In the aqueous environment, and each of these variables has been shown to have an effect on muscle contraction. 

Isotonic muscle contraction was used to measure the effects of selected nematode FaRPs on the body-wall muscle of H. contortus. AF2 was found to have inhibitory effects on muscle activity and inhibited acetylcholine (ACh) -induced contractions in the worm whereas AF8 had excitatory effects on the muscle and enhanced ACh-induced contractions (Marks et al., 1999a). There were obvious differences in the methodologies used to evaluate the effects of these peptides on Haemonchus muscle compared with those used to examine these peptide effects on Ascaris. How comparable the results are has yet to be determined. 

These drugs act by binding to Pj-adrenoceptors on myometrial cell membranes and activating adenylyl cyclase. This in turn increases levels of cAMP in the cell (Fig. 62.1), activating cAMP-dependent protein kinase, hence decreasing intracellular calcium concentrations and reducing the effect of calcium on muscle contraction. 

The effect of calcium on muscle contraction. Binding of calcium to the TN-TM-actin complex produces a shift in the location of TM, which produces an allosteric transition in actin. The allosteric transition in actin facilitates the release of P from myosin, which strengthens the interaction between actin and myosin. 

Thompson, C.S. and Mettrick, D.F. (1989) The effects of 5-hydroxytryptamine and glutamate on muscle contraction in Flymenolepis diminuta (Cestoda). Canadian Journal of Zoology 67, 1257-1262. 

Isolated tissue Blood vessels, heart, lung, ileum (rat or guinea pig) In vitro Effects on vascular contraction and relaxation selectivity for vascular receptors effects on other smooth muscles... 

Hyperglycemic peptides may have several physiological effects. A major action by all these peptides is to elevate hemolymph carbohydrate (trehalose) levels. In addition, the Pea-CAHs were isolated bas upon their actions on muscle contraction in P, americana (10-12. Bld-HrTH was isolated based upon its hypertrehalosemic action... 

Thaliporphine (0.1-100 pM), a potent vasoconstrictor, was observed to produce contractions in the isolated guinea-pig ileum in a concentration-dependent manner. These contractions were not affected by pretreatment of the ileum with tetrodotoxin, phentolamine, prazosin, propranolol, naloxone, atropine, diphenhydramine, methysergide, indomethacin or staurosporine. However, the contraction was markedly inhibited by nifedipine and verapamil, suggesting that thaliporphine produces intestinal smooth muscle contraction by a direct effect on muscle mediated by an increased Ca+2 influx through voltage-dependent Ca+2 channels [327]. 

Seitz et al. (1997b) investigated the effects of (+)-kavain on agonist-evoked contractile activity of isolated guinea-pig ileum. Table 6.1 shows the IC50 values of the inhibitory effects of (+)-kavain on muscle contractions evoked by submaximal concentrations (which produce 90 95% of maximal response, of carbachol (lOjXM), BAY K 8644 (0.3 XM), or substance P (0.05 lM). The effect of (+)-kavain on contractions evoked by the three agonists was concentration-dependent in the range between 1 XM and 1 mM. 

Synthetic AFl and AF2 have potent biological activity on the neuromuscular system of A. suum. Injection of AFl or AF2 produced a local paralysis near the injection site. In a muscle strip preparation, both AFl and AF2 produced multiple effects on muscle tension, including relaxation, contraction, and induction of rhythmic activity (196,197). Intracellular recording techniques show that AFl, at 10 -10 m, short-circuits electrical activity in inhibitory, but not excitatory motoneurons by opening channels in their membranes (194). The input resistance of these cells is drastically reduced by AFl this effect is due, at least in large part, to the presence of receptors for AFl on the inhibitory motoneuron since, when synaptic transmission is blocked with Co, the... 

Besides AFl and AF2, 16 other Ascaris FMRFamide-like peptides have been isolated and sequenced (12 sequences are shown in Table 14.2) (194-197 Cowden and Stretton, unpublished). These sequences are unique and not related by post-translational modification or, in most cases, by proteolysis they are also different from FMRFamide-like sequences reported in other organisms, whether obtained from isolated and sequenced peptides, or by deduction from the DNA sequences of genes. It is clear that there is a family of FMRFamide-like peptides in A. suum. They can be divided into several subfamilies related by sequence. Initial experiments on their bioactivity suggest that these may also be functional subfamilies. Measurements of effects on muscle tension, and on input resistance of four types of motoneurons, show that there are at least four classes of biological activity controlled by these peptides AFl and AF2 form one class that causes contraction and the generation of rhythmic activity in muscle (194,197), AF3 and AF4 cause muscle contraction (195), AF5 and AF7 reduce the input resistance of both excitatory and inhibitory motoneurons, and AFl 1 relaxes muscle and increases the input resistance of inhibitory motoneurons (Davis and Stretton, unpublished). 

Volatile fractions obtained from Ulva pertusa were tested for anthelmintic activity using santonine solution as the control. Dimethylsulfide fraction was the most powerful against the earthworms which were killed at 1,000, 2,000, and 4,000 times dilutions as compared to santonine, terpene, and carbonyl fractions [118]. The effects of volatile constituents of marine algae Ulva pertusa, Enteromorpha, Codium, and Sargassum) on muscle contraction of earthworms were also investigated. Middle... 

Assay of Adrenaline.—The hormone value of preparations may be estimated (i.) colorimetrically, by comparison of the blue colour it yields with Folin s phosphotungstate reagent (ii.) biologically, from the inhibitory effect on the contraction of a strip of involuntary muscle suspended in saline, the accelerating effect on an isolated heart, the dilating effect on a denervated iris, and the vaso-pressor response in an animal. 

Pumiliotoxin B had no apparent effect on sodium, potassium or chloride conductances or on resting membrane potential 24). The potentiative effects of pumiliotoxin B were fully manifest in preparations in which acetylcholine receptors were blocked by a-bungarotoxin. Dantrolene, an agent which appears to interfere with release of calcium from the sarcoplasmic reticulum and methoxyverapamil, a purported antagonist of calcium channels, only partially prevented the effects of pumiliotoxin B on muscle contractions. 

Figure 2. Inhibitory effect of the extract (BTJ) on spontaneous rate in the right atrium (RA) and on muscle contraction in papillary (PAP) and left atrial muscles (LA).

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