Purpose: Although it has been supposed that the NO/cyclic GMP system produces inhibitory signals to reduce the resistance of the bladder outlet and urethra during the micturition phase, little is known on the mechanisms controlling the function of urethral smooth muscle. The aim of the present study was to examine in the male and female urethra the expression of phosphodiesterase (PDE) isoenzymes, known as key proteins of the cyclic GMP/AMP signaling.
Methods: Urethral tissue was obtained from 4 female cadavers and 7 male patients (who had undergone gender reassignment surgery). The expression of mRNA encoding for PDE1A, 1B, 1C, 2A, 4B, 4D, 5A, 10A and 11A was investigated by means of real-time polymerase chain reaction. Western blot (WB) analysis was conducted to detect PDE isoenzymes.
Results: RT-PCR revealed relevant amounts of mRNA encoding for PDE1A, 2A, 4B, 5A, 10A and 11A in male and female urethral tissue. The expression of PDE1A, 2A, 4B and 10A was 2-fold higher in the female than in the male urethra, whereas the expression of PDE11A mRNA was 7-fold higher in the male tissue. In the WB experiments, immunosignals specific for PDE1A, PDE4A and 4B and PDE11A were of higher degree in the female than the male tissue specimens, while an almost equivocal expression of PDE2A, PDE5A and PDE10A was registered.
Conclusion: On the level of mRNA and function proteins, different patterns of expression of PDE isoenzymes were registered in human male and female urethra. Future studies may clarify whether inhibition of PDE isoenzymes is likely to facilitate the relaxation of the outflow region in both sexes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989682 | PMC |
http://dx.doi.org/10.2147/RRU.S291962 | DOI Listing |
World J Urol
November 2024
Hannover Medical School, Division of Surgery, Department of Urology & Urological Oncology, Hannover, Germany.
Purpose: Urolithiasis and symptomatic ureterolithiasis represent diseases known to be on the increase in most westernized countries. The present article aims to give an overview on some drug principles assumed to target signalling systems involved in modulating ureter smooth muscle contractility and to present background to their potential use or prospects in ureter stone disease.
Methods: The article reviews drugs that have been evaluated over the last decades in vitro, in vivo and/or in clinical settings with regard to their properties to achieve spontaneous passage of (distal) ureteral stones and relieve colic pain.
Pharmacol Res Perspect
February 2024
Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre-contracted with 5-HT (100 μM). Upon generation of stable phasic contractions, PDE-4 and PDE-5 inhibitors were added cumulatively to separate tissues.
View Article and Find Full Text PDFImmunotherapy
December 2023
Unit of Pharmacology, Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', 80138, Naples, Italy.
Cell Mol Neurobiol
August 2023
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, The Nilgiris, Ooty, 643001, Tamil Nadu, India.
Clinicians and researchers are exploring safer and novel treatment strategies for treating the ever-prevalent Parkinson's disease (PD) across the globe. Several therapeutic strategies are used clinically for PD, including dopamine replacement therapy, DA agonists, MAO-B blockers, COMT blockers, and anticholinergics. Surgical interventions such as pallidotomy, particularly deep brain stimulation (DBS), are also employed.
View Article and Find Full Text PDFEur J Pharmacol
April 2023
Université Paris-Saclay, Inserm, UMR-S 1180, Orsay, France. Electronic address:
Phosphodiesterases (PDE) type 3 and 4 promote vasoconstriction by hydrolysing cAMP. In experimental heart failure (HF), PDE3 makes PDE4 redundant in aorta, but it is not known if this occurs in resistance vessels, such as mesenteric artery. As PDE2 is increased in the failing myocardium, its possible role in the vasculature also needs to be addressed.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!