Immunohistochemical Localization of cGMP-binding cGMP-specific Phosphodiesterase (PDE5) in Rat Tissues

Abstract

S U M M A R YWe raised a polyclonal antibody against maltose binding protein fusion human cGMP-binding, cGMP-specific phosphodiesterase (PDE5) produced in E. coli. This antibody immunoreacted specifically with recombinant human and rat PDE5 proteins expressed in transfected COS-7 cells and with a native form of PDE5 in extracts of rat platelets, lung, and cerebellum. Immunohistochemical analysis showed that the anti-PDE5 antibody detected immunoactive materials in Purkinje cell layers of the cerebellum, proximal renal tubules, collecting renal ducts, and epithelial cells of pancreatic ducts in rats. Reverse transcriptase-polymerase chain reaction analysis demonstrated that PDE5 transcripts are also present in rat cerebellum, kidney, and pancreas. Here we described a cell-specific localization of PDE5 in various rat tissues, suggesting the possibility of the presence of a cGMP/PDE5 pathway in these tissues.

Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High Glucose-induced Matrix Protein Synthesis in Podocytes

“…PDE5 is expressed in the kidney and the glomerulus (22)(23)(24), suggesting that renal cells would be responsive to tadalafil. As expected, tadalafil increased cGMP content in the renal glomerular podocyte in this study.…”

“…Recent reports suggest that the two gasotransmitters interact in a cell-specific manner (21). In addition to NO synthases and H 2 S-generating enzymes, PDE5 has been localized to the kidney including the glomerulus (22)(23)(24), indicating that cell machinery exists for the interaction of pathways involving H 2 S and NO in renal cells. However, to our knowledge, this interaction has not been investigated in the kidney.…”

Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells

“…Both cell types have ANF receptors, and ANF increases cGMP in these cells (37). cGMP-specific phosphodiesterase V is also present in the collecting duct (38), and the PDE V inhibitor zaprinast increases cGMP in response to ANF when applied to isolated collecting ducts of rats with nephrotic syndrome (39). The effect of ANF (through an increase in cGMP) on ion and fluid transport by the collecting duct is controversial and seems also to depend on the precise collecting duct segment that is examined.…”

Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation by Abdel-Hamid et al

“…Other workers feel primary PE may be controlled by biogenic factors, 2 which may well have their basis in dysfunctional 5HT receptors in the central and peripheral nervous systems. 3,4 Although PDE5 receptors have been found in the cerebellum of rats 5 and PDE7 receptors in the caudate nucleus of humans, 6 we ®nd it implausible on a theoretical level that sildena®l has a direct effect on latency times. It is tautological to state, as they say, that`ejaculation latency time is dependent on erection time' Ð intravaginal latency time is terminated by ejaculation, so that these times (in men without erectile dysfunction) are almost always the same.…”