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Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro.
Urology. 1995 May; 45(5):893-901.U

Abstract

OBJECTIVES

This study was undertaken to characterize adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) phosphodiesterases (PDEs) in porcine detrusor smooth muscle and to define their possible role in tension regulation.

METHODS

PDEs were isolated from porcine detrusor homogenate by Q-Sepharose anion exchange and calmodulin affinity chromatography. The effects of selective inhibitors of cAMP and cGMP PDEs were investigated on isolated PDEs and on carbachol (1 microM) precontracted detrusor strips.

RESULTS

Six PDE isoenzymes were isolated by Q-Sepharose anion exchange and calmodulin affinity chromatography: one calmodulin-stimulated PDE (PDE I) which hydrolyzed mainly cGMP, one cGMP-stimulated cAMP PDE (PDE II), two cAMP-specific PDE (PDE IV alpha and IV beta), and two cGMP-specific PDE (PDE V alpha and V beta). PDE I was potently inhibited in a dose-dependent fashion by papaverine, vinpocetine, and zaprinast; the PDE IVs were potently inhibited by papaverine and rolipram; and the PDE Vs were weakly inhibited by papaverine. In organ bath studies, inhibitors of PDE III (milrinone), IV (rolipram), and V (zaprinast) caused only minor relaxations at high concentrations (200 microM), whereas papaverine and vinpocetine caused relaxations of more than 50%.

CONCLUSIONS

Our findings support the involvement of cyclic nucleotide metabolism in the regulation of the detrusor smooth muscle tone in the pig and its regulation by PDEs. The weak action of PDE IV and V inhibitors in vitro may be explained by a possible intracellular compartmentalization of such PDEs and the low cyclic nucleotide turnover rate at the conditions used.

Authors+Show Affiliations

Department of Urology, Hannover Medical School, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7747383

Citation

Truss, M C., et al. "Porcine Detrusor Cyclic Nucleotide Phosphodiesterase Isoenzymes: Characterization and Functional Effects of Various Phosphodiesterase Inhibitors in Vitro." Urology, vol. 45, no. 5, 1995, pp. 893-901.
Truss MC, Uckert S, Stief CG, et al. Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro. Urology. 1995;45(5):893-901.
Truss, M. C., Uckert, S., Stief, C. G., Schulz-Knappe, P., Hess, R., Forssmann, W. G., & Jonas, U. (1995). Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro. Urology, 45(5), 893-901.
Truss MC, et al. Porcine Detrusor Cyclic Nucleotide Phosphodiesterase Isoenzymes: Characterization and Functional Effects of Various Phosphodiesterase Inhibitors in Vitro. Urology. 1995;45(5):893-901. PubMed PMID: 7747383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro. AU - Truss,M C, AU - Uckert,S, AU - Stief,C G, AU - Schulz-Knappe,P, AU - Hess,R, AU - Forssmann,W G, AU - Jonas,U, PY - 1995/5/1/pubmed PY - 1995/5/1/medline PY - 1995/5/1/entrez SP - 893 EP - 901 JF - Urology JO - Urology VL - 45 IS - 5 N2 - OBJECTIVES: This study was undertaken to characterize adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) phosphodiesterases (PDEs) in porcine detrusor smooth muscle and to define their possible role in tension regulation. METHODS: PDEs were isolated from porcine detrusor homogenate by Q-Sepharose anion exchange and calmodulin affinity chromatography. The effects of selective inhibitors of cAMP and cGMP PDEs were investigated on isolated PDEs and on carbachol (1 microM) precontracted detrusor strips. RESULTS: Six PDE isoenzymes were isolated by Q-Sepharose anion exchange and calmodulin affinity chromatography: one calmodulin-stimulated PDE (PDE I) which hydrolyzed mainly cGMP, one cGMP-stimulated cAMP PDE (PDE II), two cAMP-specific PDE (PDE IV alpha and IV beta), and two cGMP-specific PDE (PDE V alpha and V beta). PDE I was potently inhibited in a dose-dependent fashion by papaverine, vinpocetine, and zaprinast; the PDE IVs were potently inhibited by papaverine and rolipram; and the PDE Vs were weakly inhibited by papaverine. In organ bath studies, inhibitors of PDE III (milrinone), IV (rolipram), and V (zaprinast) caused only minor relaxations at high concentrations (200 microM), whereas papaverine and vinpocetine caused relaxations of more than 50%. CONCLUSIONS: Our findings support the involvement of cyclic nucleotide metabolism in the regulation of the detrusor smooth muscle tone in the pig and its regulation by PDEs. The weak action of PDE IV and V inhibitors in vitro may be explained by a possible intracellular compartmentalization of such PDEs and the low cyclic nucleotide turnover rate at the conditions used. SN - 0090-4295 UR - https://www.unboundmedicine.com/medline/citation/7747383/Porcine_detrusor_cyclic_nucleotide_phosphodiesterase_isoenzymes:_characterization_and_functional_effects_of_various_phosphodiesterase_inhibitors_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-4295(99)80103-4 DB - PRIME DP - Unbound Medicine ER -