THE EFFECTS OF CLONIDINE ON ELECTRICALLY‐INDUCED CONTRACTIONS OF RAT DETRUSOR STRIPS IN VITRO

Abstract
Clonidine (10-9.sbd.3 .times. 10-6 M) produced a concentration dependent inhibition of field stimulation-induced contractions of rat detrusor muscle strip at 0.1 and 1 Hz which were completely abolished by tetrodotoxin (5 .times. 10-7 M) but were unaffected by hexamethonium (10-5 M). Pretreatment with yohimbine (10-8.sbd.10-7 M) did not modify the amplitude of contractions but produced a rightward parallel shift of clonidine''s cumulative response curve without a depression of the maximal response. The corresponding pA2 [competitive antagonistic activity] value for yohimbine was 8.44 .+-. 0.1. Atropine (3 .times. 10-6 M) produced a partial inhibition of contractions at both frequencies. In the presence of atropine the cumulative response curve of clonidine was significantly reduced at 1 but not at 0.1 Hz. Indomethacin (5 .times. 10-5 M) and theophylline (2 .times. 10-4 M) produced a partial inhibition of amplitude of contractions at both frequencies without any interference with the effect of a supramaximal concentration of clonidine. Prazosin (10-6 M), propranolol (10-6 M), chlorpheniramine (10-6 M), ranitidine (10-6 M), haloperidol (10-7 M), pizotifen (10-6 M), naloxone (10-6 M), quinidine (10-6 M), strychnine (10-5 M) or picrotoxin (10-5 M) neither affected the amplitude of contractions at either frequency nor antagonized clonidine effects. The contractile response of non stimulated strips to acetylcholine (10-5 M), carbachol (3 .times. 10-6 M) and ATP (10-3 M) were not significantly influenced by pretreatment with clonidine (3 .times. 10-6 M). Evidently, stimulation of prejunctional .alpha.2-adrenoceptors located on postganglionic nerve endings might reduce the output of excitatory neurotransmitter(s) in rat urinary bladder.