Inhibition of the contractile response of the rat detrusor muscle by the beta(2)-adrenoceptor agonist clenbuterol.
The action of clenbuterol, beta(2)-adrenoceptor agonist, on the contractile response of isolated rat detrusor muscle strips was investigated in vitro. Clenbuterol (10(-5) M) inhibited the detrusor muscle frequency response (1-40 Hz, p<0.02) with a more pronounced effect at 1 Hz than 40 Hz. Clenbuterol (10(-6) M) significantly inhibited the contractile response to exogenous ATP (10(-4) to 10(-2) M, p<0.05) but not to carbachol (10(-9) to 10(-4) M). The presence of 10(-5) M ICI 118, 551, beta(2)-adrenoceptor antagonist, shifted significantly the clenbuterol dose-response to 1 Hz electrical field stimulation (EC(50) 3.4x10(-6) M (+/-2.2x10(-6) M) for clenbuterol alone, to 4.1x10(-4) M (+/-8.8 x10(-5) M), P<0.05). In conclusion, clenbuterol inhibits electrical field and ATP-stimulated contractions of detrusor muscle. Reversal of the clenbuterol inhibition of detrusor muscle contraction by ICI 118, 551 shows that clenbuterol is probably acting through postsynaptic beta(2)-adrenoceptors, which modulate the response to ATP released from purinergic nerves.
Hudman
D
D
Department of Medicine, Division of Medicine for the Elderly, University of Leicester, Leicester General Hospital, Leicester, UK. dh35@le.ac.uk
Elliott
R A
RA
Norman
R I
RI
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D013779:Tetrodotoxin; C026777:ICI 118551; D000255:Adenosine Triphosphate; D002217:Carbachol; D002976:Clenbuterol