Cimaterol reduces β-adrenergic receptor density in rat skeletal muscles

Abstract

Interactions between the beta-adrenoceptor agonist cimaterol and beta-adrenoceptors on rat skeletal muscle membranes were examined in two studies. In Exp. 1, muscle samples from eight Sprague-Dawley rats (female, approximately 200 g) were used for competition binding and autoradiographic studies using [125I]cyanopindolol (ICYP) as a radioligand. The affinities or dissociation constants for binding (KD values) for cimaterol in plantaris and soleus muscles were .68 and .92 microM, respectively. Muscle areas stained for succinic dehydrogenase had propranolol-resistant ICYP binding sites; cimaterol did not seem to compete for these sites. In Exp. 2, 60 Sprague-Dawley rats (female, approximately 218 g) were fed 0 or 10 ppm of cimaterol in rat diet that was ground. Groups were killed after 1, 3, 7, 14, or 28 d of treatment. Cimaterol increased BW gain up to 14 d after commencement of treatment, with little or no improvement thereafter. Enhanced weight gain in skeletal muscles also occurred up to 14 d of cimaterol treatment. Densities of beta-adrenoceptors in plantaris and soleus muscle membrane homogenates were estimated using a radioligand binding assay with ICYP. A significant reduction in the number of binding sites (Bmax) was observed after 3 d of cimaterol treatment in plantaris muscle without a change in the KD of ICYP binding. The percentage reductions in Bmax were 26.8, 42.2, 37.7, and 37.8% at 3, 7, 14, and 28 d after cimaterol administration, respectively. In the soleus muscle, significant reductions (44.1 and 29.8%) in Bmax were observed after 3 and 14 d of cimaterol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenergic receptors in skeletal muscles of ruminants: Effects of temperature and feed intake

“…That the Scatchard plots for specific binding were linear, and the equilibrium binding data did not fit a twosite model of Graphpad Prism, implies that there was no negative co-operativity or the presence of multiple binding sites as was reported for binding of DHA to rat adipocyte membranes (Dax et al 1982). These results are similar to those of Kim et al (1992), and , who reported that DHA binding to rat skeletal muscle membranes was saturable and Scatchard analysis revealed that DHA binds to a single class of receptor sites. For personal use only.…”

“…However, Elfellah and Reid (1987) concluded that β-adrenergic receptors (β-AR) in skeletal muscles (gastrocnemius and soleus) of pigs are predominantly, if not exclusively, of the β2 subtype. Furthermore, soleus muscle of cat (Minneman et al 1979), bovine musculus trapezium (Ijzerman et al 1984) and plantaris muscles of rats (Kim et al 1992) were found to have only the β2 subtype. However, rat soleus muscle (Kim et al 1992) was found to have both β1 and β2 AR, similar to the results obtained for the skeletal muscles of sheep.…”

“…Furthermore, soleus muscle of cat (Minneman et al 1979), bovine musculus trapezium (Ijzerman et al 1984) and plantaris muscles of rats (Kim et al 1992) were found to have only the β2 subtype. However, rat soleus muscle (Kim et al 1992) was found to have both β1 and β2 AR, similar to the results obtained for the skeletal muscles of sheep. The adrenergic properties of a muscle are a reflection of their fibre type (Elfellah and Reid 1987), and differences in fibre types (see below) can, in part, explain the different adrenergic receptor distribution obtained for the same muscle in different species.…”

Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training

“…is probably due to the higher downregulation of ␤ 2 -adrenoceptors in red than white muscles (17,21). ␤ 2 -Adrenoceptor activation, through ␤ 2 -agonists, increases twitch-tension and glycogenolysis in fast fibers (20,41).…”

“…Although short-term use of ␤ 2 -adrenoceptor agonists has been recommended for therapeutic purposes related to functional recovery after skeletal muscle trauma (3), chronic administration of sympathomimetics leads to ␤ 2 -adrenoceptormediated skeletal myotoxicity and loss of its potential muscular benefits (21,29). In fact, we observed that chronic sympathetic hyperactivity induced skeletal muscle myopathy in 7-mo-old ␣ 2A /␣ 2C ARKO mice associated with a more extensively prooxidant state marked by increased muscular norepinephrine levels associated with decreased redox balance and increased lipid hydroperoxidation and iNOS expression.…”