title: Acute inhibitory effects of clenbuterol on force, Ca²⁺ transients and action potentials in rat soleus may not involve the β₂-adrenoceptor pathway.
abstract: 1. Clenbuterol, a β(2)-adrenoceptor agonist, can have inhibitory and myotoxic effects on slow-twitch muscles. Clenbuterol is lipophilic and may enter into the intracellular compartment, and because of this, it is likely that clenbuterol will have different effects to classical β(2)-adrenoceptor agonists such as terbutaline. The aim of the present study is to investigate clenbuterol's effect on force, intracellular [Ca(2+)] and electrophysiology, and the role of the β(2)-adrenoceptor pathway in these effects. 2. Simultaneous measurements of isometric force and [Ca(2+)](i) were made from small bundles of rat soleus muscle fibres in which several superficial fibres had been pressure-injected with the fluorescence Ca(2+) indicator Indo-1. The muscle's electrophysiological response was measured using glass intracellular microelectrodes. 3. The most robust effect of clenbuterol was a concentration- (10-50 μmol/L) and frequency-dependent (10-80 Hz) loss of force and [Ca(2+)](i) maintenance during tetanic stimulation of muscle fibres. None of these effects were reduced in the presence of the β(2)-antagonist ICI 118551. 4. In addition clenbuterol had a significant effect on muscle electrophysiology, with action potentials measured during tetanic trains being inhibited in a concentration- and frequency-dependent manner. This response was also unchanged by pre-treatment with the β(2)-antagonist ICI 118551. 5. These results indicate that some of clenbuterol's effects are mediated through a pathway other than the β(2)-adrenoceptors.
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Stewart I
authors.initials: SI
authors.lastname: Head
authors.forename: Tuyen N V
authors.initials: TN
authors.lastname: Ha
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002976:Clenbuterol / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D007211:Indoles; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; C048960:indo-1; D011188:Potassium; D002118:Calcium; D002976:Clenbuterol