Inhibition of the contractile response of the rat detrusor muscle by the β2-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 (EC50 3.4 X 10(-6) M (+/-2.2 X 10(-6) M) for clenbuterol alone, to 4.1 X 10(-4) M (+/- 8.8 X 10(-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. (C) 2000 Elsevier Science B.V. All rights reserved.