Cyclic nucleotide phosphodiesterases in rabbit detrusor smooth muscle

Abstract

Objectives: To identify the phosphodiesterase (PDE) isoenzymes in the rabbit detrusor and to evaluate their roles in regulating detrusor muscular tone. Cyclic nucleotides are important secondary messengers involved in modulating the contractility of various smooth muscles. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are synthesized by their respective cyclases and degraded by various PDEs.

Methods: PDE isoenzymes from male and female rabbit detrusor were isolated by the Mono-Q anion exchange column and identified with various inhibitors. Detrusor strips from both sexes were precontracted with carbachol and relaxed with PDE inhibitors and adenylate and guanylyl cyclase activators in a tissue bath. Cyclic nucleotide concentrations in strips from male rabbits were determined after the compound treatment.

Results: Similar results were obtained from both sexes in the experiments in which both sexes were used. The activities of PDE1, 2, 3, 4, and 5 were identified. Forskolin induced a dramatic rise in the cAMP levels and was the most effective relaxant. Papaverine generated moderate increases in the cAMP and cGMP levels and induced very good relaxation. Vinpocetine produced no detectable changes in the cyclic nucleotide levels but elicited good relaxation. Sildenafil caused an increase in the cGMP levels and had a similar relaxation effect as vinpocetine. Sodium nitroprusside induced some increase in cGMP and had no relaxation effect. Rolipram raised the cAMP levels significantly, yet had a moderate effect on relaxation.

Conclusions: Our results demonstrated the presence of PDE1 through 5 in rabbit detrusor muscle and supported their involvement in regulating detrusor muscle tone. The relaxation of rabbit detrusor was mainly mediated by the cAMP pathway.