Cimaterol reduces beta-adrenergic receptor density in rat skeletal muscles.
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)
Kim
Y S
YS
School of Agriculture and Forestry, University of Melbourne, Parkville, Victoria, Australia.
Sainz
R D
RD
Summers
R J
RJ
Molenaar
P
P
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D004983:Ethanolamines / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008024:Ligands; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013194:Staining and Labeling; D013385:Succinate Dehydrogenase; D015430:Weight Gain / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D008024:Ligands; D011943:Receptors, Adrenergic, beta; D013385:Succinate Dehydrogenase; C047411:cimaterol