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Most of the localization studies for PDE11 have been for PDE11A mRNA products. The data for protein are less certain as few highly specific antisera have been described. There also is likely to be substantial differences in expression between species. Nevertheless, it is clear that the PDE11A variants demonstrate differential tissue expression. In humans, PDE11A1 mRNA is most prominent in skeletal muscle and prostate (Fawcett et al., 2000; Yuasa et al., 2001a). PDE11A3 mRNA is found specifically in testis and PDE11A4 mRNA is highly expressed in prostate (Yuasa et al., 2000). PDE11A protein localization studies have been somewhat contradictory in their findings, probably because of differences in the specificity of the antibodies used. PDE11A1 protein was originally detected in prostate and skeletal muscle (Fawcett et al., 2000), although a later study did not detect PDE11A1 protein in any tissues (Loughney et al., 2005). In fact, only PDE11A4 protein has been verified and is found in prostate, pituitary, heart, and liver. Another study suggested that PDE11A is widely expressed, and immunohistochemistry using an antibody reported to recognize all PDE11A variants localized it to the epithelial, endothelial, and smooth muscle cells of many tissues, but at highest levels in the prostate, testis, kidney, adrenal gland, colon, and skin (D'Andrea et al., 2005). However, a separate study did not find any PDE11 protein expression in human testis (Loughney et al., 2005). As with many PDEs, it is still not clear if the same tissue, cellular, and subcellular localization is found among species. Future work will hopefully rectify the discrepancies regarding the tissue expression of PDE11A.
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BALB/c splenocytes were stained either with 5 µM CFSE (Invitrogen) for 10 min at 37°C and pulsed with the relevant AH-1 MHC class I peptide (corresponding to amino acids 423–431 of gp70, SPSYVYHQF; CFSEhigh cells) or with 0.5 µM CFSE and pulsed with an irrelevant peptide (HA) as a control (CFSElow cells). 107 splenocytes (per population) were transferred i.v. to each host. The draining inguinal lymph nodes and spleens were harvested 40 h later and analyzed by FACS. Percent lysis was calculated as 1 – CFSEhigh/CFSElow normalized by the same ratio in naive BALB/c mice (%lysis = 100 x {1 – [(CFSEhighexp/CFSElowexp)/(CFSEhighBALB/c/CFSElowBALB/c)]}).
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TABLE 5 Multi-isoform inhibitors and secondary targets of selective inhibitors Although many inhibitors are called “selective”, this is really a relative term. The compounds are termed selective based on the fact that other isoforms are only inhibited at higher concentrations. Some compounds such as dipyridamole and zardaverine are selective for a limited number of isoforms. However, some of the inhibitors that target multiple isoforms may be useful because of this property. For example, dipyridamole is a component of the stroke treatment Aggrenox (aspirin/extended-release dipyridamole).
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About four percent of participants had RLS (944 of 23,119 men), and about 41 percent (9,433 men) had erectile dysfunction. Men with RLS were older and were more likely to be Caucasian. The prevalence of erectile dysfunction also increased with age.
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