DIAZEPAM, ADENOSINE-ANALOGS AND CALCIUM-CHANNEL ANTAGONISTS INHIBIT THE CONTRACTILE ACTIVITY OF THE MOUSE URINARY-BLADDER

The main neurotransmitter of the mouse urinary bladder is ATP, which i s hydrolyzed to AMP and adenosine; the latter compound, in contrast to ATP, relaxes the smooth muscle. Diazepam also relaxes the urinary bla dder and, since some peripheral and central effects of the benzodiazep ines are thought to be induced by inhibition of adenosine uptake or by inhibiting calcium channels, the effects of diazepam, adenosine, R-ph enylisopropyladenosine, cyclohexyladenosine, and of the calcium channe l antagonists, diltiazem, verapamil and nifedipine, were studied on th e contractile responses of the mouse isolated urinary bladder. The con tractile responses of the bladder's smooth muscle were elicited by tra nsmural stimulation and by application of ATP or acetylcholine. All dr ugs mentioned decreased the contractile responses of the bladder. The inhibitory effect of diazepam was similar to that induced by adenosine , R-phenylisopropyladenosine, cyclohexyladenosine, and nifedipine. 8-P henyltheophylline, an adenosine receptor antagonist, did not decrease the relaxatory response of diazepam, which might exclude a P-1 purinoc eptor-mediated mechanism in the response studied. Diazepam did not sig nificantly change the inhibitory effects of diltiazem and nifedipine o n the contractile response to acetylcholine. The similar patterns of r elaxant effects, exerted by diazepam, adenosine analogues and calcium channel antagonists, suggest the interference of benzodiazepine, and a denosine and its analogues on calcium channels of the urinary bladder smooth muscle. The inability of diazepam to further increase the effec ts of diltiazem and nifedipine on the responses to acetylcholine, rein forces the hypothesis that diazepam is acting through a common mechani sm with calcium antagonists.