Effect of cromakalim on the purinergic and cholinergic transmission in the rat detrusor muscle.
Contraction of the rat detrusor muscle is mediated by cholinergic and purinergic mechanisms. The present study was carried out to look at the influence of cromakalim, compared with atropine, suramin and nifedipine on the contractile response evoked by single shock and exogenous agonists (carbachol and ATP) in rat urinary bladder. Cromakalim was able to inhibit only partially the response to carbachol and profoundly affected the response to exogenous ATP. Atropine suppressed the response to carbachol and was inactive versus ATP. Suramin was inactive versus carbachol and was able to antagonize the response to ATP. Nifedipine proved to be a non-competitive antagonist versus carbachol (pD2 = 7.66 +/- 0.05) and deeply affected the response to ATP. Cromakalim inhibited only partially the first, purinergic, phase of the electrically evoked response but was able to inhibit in a concentration-dependent manner the second, cholinergic, phase (logIC50 = 6.87 +/- 0.05). Nifedipine blocked both the phases. Atropine blocked partially only the second phase. Suramin inhibited the first phase but, at least partially, also the second one. The combination of atropine and suramin enhanced the inhibition of the second phase. The antagonistic effect of suramin on the second phase could indicate an overlap of the purinergic and cholinergic components. The comparison between pre- and postjunctional effects indicates that cromakalim acts on purinergic transmission predominantly postjunctionally. On the contrary, the action on cholinergic transmission seems to occur mainly at prejunctional level. This conclusion can be relevant in view of the claimed importance of K+ channel openers in the treatment of urinary disorders.
Boselli
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C
Istituto di Farmacologia, Facoltà di Farmacia, Università di Pavia, Italy.
Bianchi
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L
Grana
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E
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
D011950:Receptors, Cholinergic; D011983:Receptors, Purinergic; D019806:Cromakalim; D000255:Adenosine Triphosphate; D002217:Carbachol; D009543:Nifedipine