Diazepam, adenosine analogues and calcium channel antagonists inhibit the contractile activity of the mouse urinary bladder.
The main neurotransmitter of the mouse urinary bladder is ATP, which is hydrolyzed to AMP and adenosine; the latter compound, in contrast to ATP, relaxes the smooth muscle. Diazepam also relaxes the urinary bladder and, since some peripheral and central effects of the benzodiazepines are thought to be induced by inhibition of adenosine uptake or by inhibiting calcium channels, the effects of diazepam, adenosine, R-phenylisopropyladenosine, cyclohexyladenosine, and of the calcium channel antagonists, diltiazem, verapamil and nifedipine, were studied on the contractile responses of the mouse isolated urinary bladder. The contractile responses of the bladder's smooth muscle were elicited by transmural stimulation and by application of ATP or acetylcholine. All drugs 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-Phenyltheophylline, an adenosine receptor antagonist, did not decrease the relaxatory response of diazepam, which might exclude a P1 purinoceptor-mediated mechanism in the response studied. Diazepam did not significantly change the inhibitory effects of diltiazem and nifedipine on the contractile response to acetylcholine. The similar patterns of relaxant effects, exerted by diazepam, adenosine analogues and calcium channel antagonists, suggest the interference of benzodiazepine, and adenosine and its analogues on calcium channels of the urinary bladder smooth muscle. The inability of diazepam to further increase the effects of diltiazem and nifedipine on the responses to acetylcholine, reinforces the hypothesis that diazepam is acting through a common mechanism with calcium antagonists.
Departamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, Chile.
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Schaufele
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Schumacher
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CG
Acevedo
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E
Contreras
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009125:Muscle Relaxants, Central; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D000241:Adenosine; D000109:Acetylcholine; D003975:Diazepam; D011188:Potassium; D002118:Calcium