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Biomedical subjects

C A Maltin

Publications and source records attributed to C A Maltin.

At least 37 records · Page 2Linked to original sources
PubMed1993

Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients.

1. The sympathomimetic agent clenbuterol has a muscle-specific anabolic effect in normal and wasted muscles from animals. This trial was designed to examine the effect of the drug on the recovery of muscle strength and area after open medial meniscectomy. 2. A double-blind, completely randomized, placebo-controlled study was carried out on 20 healthy male patients. Muscle strength and cross-sectional area were determined before and after surgery. Patients were treated with drug or placebo for 4 weeks postoperatively and there was a 2 week washout period. 3. The results suggest that, in the operated leg, clenbuterol treatment is associated with a more rapid rehabilitation of strength in knee extensor muscles; in the unoperated leg, knee extensor strength increased above the initial values after 6 weeks (P = 0.01). However, in terms of absolute strength the differences were not significant between the two groups. 4. It is concluded that the data lend support to the proposition that clenbuterol has therapeutic potential in the treatment of muscle-wasting conditions.

Adult↗
PubMed1993

Clenbuterol mimics effects of innervation on myogenic regulatory factor expression.

The amelioration of denervation atrophy by the beta-adrenoceptor agonist clenbuterol has led to the suggestion that the drug mimics or stimulates production of neurotrophic factors. Neurotrophic factors have profound effects on muscle growth, but the precise mechanisms through which this influence is exerted are unknown. The expression of myoD and myogenin, proteins that in turn regulate the transcription of tissue-specific genes during skeletal muscle differentiation, is controlled by innervation. In muscle undergoing denervation-induced atrophy, myoD and myogenin mRNAs increase. However, this is only partially reversed by electrical activity, thus implicating neurotrophic factors in regulation of these genes. Here we demonstrate that clenbuterol represses myoD and myogenin expression and decreases the levels of acetylcholine receptors in denervated muscles. The data provide the first evidence that the action of clenbuterol is directed through the neural axis.

Animals↗
PubMed1993

Calcitonin gene related peptide stimulates differentiation of neonatal rat myogenic cultures.

The effect of the nerve derived peptide, calcitonin gene related peptide (CGRP) on myoblast fusion/differentiation was studied in rat myogenic cell cultures, using creatine kinase activity as an index of fusion. Addition of CGRP at 10(-7) M to myoblast cultures resulted in an enhancement of kinase activity after 11 days of treatment. This response was not accompanied by increased protein content of cultures implying an effect primarily on fusion rather than on myotube growth/size. Neither was it a direct effect on enzyme activity alone since no increase in creatine kinase activity occurred when CGRP was added to mature myotube cultures. These data suggest a role for CGRP in the myoblast fusion process itself and raise questions as to its importance in the growth and development of muscle in vivo.

Animals↗
PubMed1992

Denervation increases clenbuterol sensitivity in muscle from young rats.

Clenbuterol has been shown to ameliorate denervation-induced atrophy and, therefore, clearly has therapeutic potential in the treatment of muscle wasting conditions in man. Previous studies have used dosages in rats which would be unacceptable in clinical practice, but the present results show that denervated muscle has a greater sensitivity to the drug than innervated or cardiac muscle. Fiber hypertrophy and an increase in protein and RNA content could be observed in denervated muscles but not in innervated muscles at a dose of 10 micrograms/kg body weight. When considered on a metabolic body weight basis, the effective dose in rats and the "safe" dose in man are surprisingly comparable. The observations imply that there is good reason to suppose that clenbuterol could be effective in ameliorating similar wasting conditions in man.

Animals↗
PubMed1992

Effect of clenbuterol on protease activities and protein levels in rat muscle.

To elucidate the biochemical mechanism by which the sympathomimetic agent clenbuterol promotes skeletal muscle growth, we have determined the activity of a range of proteolytic enzyme types (acid, neutral and alkaline proteinases and peptidases), together with the levels of soluble and structural proteins (via SDS-polyacrylamide gel electrophoresis) in 5 innervated and denervated muscle types from control and drug-treated rats. No gross change in activity was found for any enzyme type in any muscle (innervated or denervated) following clenbuterol treatment; however, one enzyme, arginyl aminopeptidase, showed a small but consistent decrease in activity in all of the innervated muscles investigated. Similar fractionation profiles were obtained for structural or soluble proteins from corresponding muscle types (innervated or denervated) in control or clenbuterol-treated animals, with the exception of cardiac muscle, which showed a 50% increase in staining intensity of one band (subunit molecular mass 18 kD). We conclude that the anabolic action of clenbuterol in promoting skeletal muscle growth does not occur via downregulation of protease activity, or increase in levels of individual muscle proteins.

Animals↗
PubMed1992

Satellite cells in innervated and denervated muscles treated with clenbuterol.

The sympathomimetic agent, clenbuterol, induces a muscle-specific hypertrophy in both normal and catabolic muscle. Drug-induced hypertrophy is not generally associated with an increase in DNA content, thus the role of satellite cells in the response of soleus muscles from weanling rats is questioned. Following simultaneous sciatic section and administration of clenbuterol, responses are similar in innervated and denervated muscles after 4 days. Increased protein accretion in treated muscles is associated with evidence of satellite cell activation, but with little evidence of division. It is speculated that satellite cell production of growth factors may play an important role in the hypertrophic action of clenbuterol, and the clinical implications of the findings are discussed.

Animals↗
PubMed1992

Stimulation of actin and myosin synthesis in rat gastrocnemius muscle by clenbuterol; evidence for translational control.

1. A transient rise in fractional rates of protein and actomyosin synthesis was observed in gastrocnemius muscles of rats fed clenbuterol for 1-2 days but the muscle RNA:protein ratio was unchanged, therefore protein synthesis per unit RNA (kRNA) also increased. 2. Myosin heavy and light chains and actin showed increased incorporation of [3H]phenylalanine at 2 days; these changes were proportional to increases in total protein synthesis. 3. The ratios actin mRNA:18S RNA and fast myosin heavy chain mRNA:18S RNA were unaffected by clenbuterol. 4. The data suggest that the clenbuterol-induced increase in muscle protein synthesis involves both translational control and increased tissue RNA.

Actins↗
PubMed1992

The effect of the beta-adrenergic agonist clenbuterol on growth and protein metabolism in rat muscle cell cultures.

Cultures were established from neonatal rat muscle cells, satellite cells, and L6 myoblasts and changes in protein metabolism were determined as development proceeded. For all three cell types, culture protein content increased with increasing myotube content. The beta-adrenergic agonist clenbuterol (added to a final concentration of 10(-7) M) significantly stimulated fusion (as indicated by creatine kinase activity) in neonatal muscle cultures and also increased culture protein content. This was associated with a stimulation in both the fractional (ks, percentage/day, +13%, P less than .05) and absolute (As, micrograms/day, +19%, P less than .05) rates of protein synthesis within 24 h after drug administration. At 48 h, As was increased by 42% above that of controls (P less than .01). In contrast, in satellite cell cultures, clenbuterol had no consistent effects on either protein accretion, creatine kinase activity, or protein synthesis (ks and As). Similarly, the drug had no stimulatory effect on protein synthesis and protein accretion in L6 myoblast or L6 myotube cultures (and no effect in neonatally derived fibroblast cultures). It is concluded that the fusion response to clenbuterol and, therefore, changes in protein metabolism and protein accretion are greatly dependent on the origin and genetic integrity of muscle cells.

Animals↗
PubMed1992

Tissue specific responses to clenbuterol; temporal changes in protein metabolism of striated muscle and visceral tissues from rats.

The beta-adrenoceptor agonist, clenbuterol, was administered orally to male weanling rats for a period of up to 10 days. The composition and fractional rate of protein synthesis (Ks) in skeletal and cardiac muscle, gut and liver were determined. There were few changes in the visceral tissues, but there was marked protein accretion in the muscles. The results suggested that in skeletal muscles there is an increase in both Ks and the amount of protein synthesised per unit RNA. In cardiac muscle, the results indicated that there was only a very transient increase in Ks and that changes in translational capacity (RNA/prot) may account in part for the increase in protein content. It is concluded that the mechanistic basis for the increased protein gain may be different between skeletal and cardiac muscles.

Animals↗
PubMed1990

Effects of bovine pituitary growth hormone alone or in combination with the beta-agonist clenbuterol on muscle growth and composition in veal calves.

Twenty-three British Friesian bull calves at approximately 7 d of age were allocated to one of four treatments: controls untreated (five calves), a group (Clen) given 1 mg clenbuterol/kg diet (five calves), a group (GH) given a daily subcutaneous injection of 3.5 mg bovine pituitary growth hormone (GH) (five calves) and a group (Clen + GH) given a combination of clenbuterol as in the Clen group with GH as in the GH group (seven calves). All calves were given milk-substitute at levels adjusted weekly according to metabolic live weight. The animals were slaughtered over the weight range 150-170 kg. Samples of semimembranosus and triceps muscles were excised at slaughter. Treatment with GH produced approximately a threefold increase in mean daily serum GH concentration. Calves given Clen + GH were heaviest at slaughter and the combined treatment produced a significantly higher (P less than 0.01) feed conversion ratio. Administration of clenbuterol either alone or in combination with GH increased the cross-sectional area of both fast twitch glycolytic (FG), and fast twitch oxidative glycolytic (FOG) fibres in both muscles. In contrast GH produced little change in fibre size in semimembranosus muscle, although FOG fibres in triceps were slightly larger than in controls. Neither Clen nor GH resulted in any change in fibre percentage frequency in either muscle. Treatments involving clenbuterol produced a significant decrease in muscle glycogen concentration. Muscles from all three treatment groups tended to show small increases in protein and RNA concentration compared with the controls. Muscles from animals treated with GH alone exhibited an increase in DNA concentration not seen in muscles from the two other treatment groups. Overall, the differential response to the two agents suggested that clenbuterol does not mediate its effects via the GH axis, and that an additive response in terms of protein anabolism may be achieved from the use of a combination of clenbuterol plus GH.

Animals↗
PubMed1990

Effects of the cyclo-oxygenase inhibitor, fenbufen, on clenbuterol-induced hypertrophy of cardiac and skeletal muscle of rats.

1. When rats were fed with clenbuterol for 7 days skeletal muscle mass increased by 21% in the tonic soleus and phasic plantaris muscles and a 16% hypertrophy of the heart was also induced. Fenbufen, fed to rats for the same period, blocked the hypertrophy of the heart but not that of the skeletal muscles. 2. When feeding of fenbufen commenced 3 days before the administration of clenbuterol, plasma prosta-glandin F2 alpha (PGF2 alpha) was reduced by 79%; there was again no effect of fenbufen on clenbuterol-induced increases in the RNA or protein content of plantaris, nor in the increased area of fast or slow twitch fibres in the soleus. In the heart the clenbuterol-induced increases in the RNA (+21%) and protein content (+20%) were totally inhibited. 3. The effects of clenbuterol on heart muscle appear to be mediated by a cyclo-oxygenase metabolite of arachidonic acid whilst the effects on skeletal muscle are not.

Animals↗
PubMed1990

The effect of clenbuterol administration in utero and throughout lactation on pre- and post-natal muscle development in the rat.

The beta-adrenergic agonist, clenbuterol was fed to pregnant rats during gestation and throughout lactation. Changes in muscle morphology and composition were studied in foetal and weanling rats. Drug treatment did not affect mean foetal number, but mean foetal body weight was significantly reduced. Heart weights were increased and both muscle weight and secondary to primary fibre ratios were decreased in foetuses exposed to clenbuterol in utero. In animals exposed to clenbuterol throughout gestation and lactation, muscle weights, and protein, RNA and DNA content and total fibre numbers were reduced. In addition a drug induced anabolism was observed in the muscles of the dams. The data are discussed in terms of a direct drug effect on immature and differentiated muscle together with a possible indirect action through the repartitioning action of clenbuterol.

Adenosine Triphosphatases↗
PubMed1989

The action of the beta-agonist clenbuterol on protein metabolism in innervated and denervated phasic muscles.

1. Clenbuterol treatment in innervated and denervated phasic extensor digitorum longus, plantaris and gastrocnemius muscles from rats caused a significant increase in RNA and protein contents in all muscles except denervated extensor digitorum longus. 2. All muscles showed an increase in the fractional rate of protein synthesis (Ks) with clenbuterol, but the temporal response varied. 3. The data suggest that the effect of clenbuterol on protein metabolism in innervated muscles is muscle-type specific, and demonstrate the homology of response for denervated muscles.

Animals↗
PubMed1989

Evidence that the hypertrophic action of clenbuterol on denervated rat muscle is not propranolol-sensitive.

1. The effect of propranolol on the clenbuterol-induced protein anabolism in innervated and denervated soleus and plantaris muscles of the rat was studied. 2. The response to the beta-agonist, clenbuterol, in both innervated and denervated muscles, was not significantly inhibited by the beta-antagonist, propranolol. 3. The results provide further evidence to suggest that the action of clenbuterol on skeletal muscle protein accretion may not be directly mediated by beta-adrenoceptors.

Animals↗
PubMed1989

Fiber-type composition of nine rat muscles. I. Changes during the first year of life.

There are few data available that describe the changes in fiber-type profiles with age in a range of muscles; thus fiber-type profiles and areas were determined in nine muscles of female rats from weaning to 1 yr. The results not only demonstrated the difference in fiber-type composition, size, and hence functional area in the various muscles examined but also illustrated the changes in these parameters with age. In particular, it was clear that two ends of a spectrum of fiber compositions are represented in the muscles studied: tensor fasciae latae, mainly fast-twitch glycolytic at one end and soleus (and adductor longus), mainly slow-twitch oxidative at the other; the remaining muscles were mostly dominated by fast-twitch fibers of a variety of metabolic types. Aging resulted in an increase in fiber area that was most dramatic in fast-twitch glycolytic fibers. Changes in fiber type with age were noted in all muscles, but the exact nature of the developmental changes appeared muscle specific.

Aging↗
PubMed1989

Fiber-type composition of nine rat muscles. II. Relationship to protein turnover.

Rates of protein synthesis in vivo and fiber-type composition were measured in nine limb muscles of female rats at ages ranging from weaning to 1 yr. In all muscles, there was a decline in protein synthesis with increasing age, mostly as a result of a fall in the RNA content. Rates of protein breakdown and growth were determined in six muscles and these also declined with age. Regression analysis of the data for all ages showed that protein synthesis was correlated with the content of slow oxidative fibers but not with the relative proportions of fast glycolytic to fast oxidative glycolytic fibers.

Aging↗
PubMed1987

Clenbuterol, a beta agonist, induces growth in innervated and denervated rat soleus muscle via apparently different mechanisms.

Dietary administration of the anabolic agent, clenbuterol, has already been shown to inhibit or reverse denervation-induced atrophy in rat soleus muscles. We now show that the ameliorative effects of clenbuterol in denervated rat muscles are due principally to a large increase in protein synthesis. This results from both an increase in protein synthetic capacity and a normalised translational efficiency. The responses of innervated and denervated muscles are therefore fundamentally different, the changes in denervated muscles being reminiscent of the classical pleiotypic response of cells to growth factors.

Animals↗