Disease relevance of PDE8A

• The C-terminal 545 amino acids of PDE8A (the region shared among all splice variants) were expressed in baculovirus [1].

High impact information on PDE8A

• A 4-fold increase in the sensitivity to LH for testosterone production was detected in Leydig cells isolated from PDE8A knockout mice [2].
• These observations indicate that PDE8A and at least one other PDE control the same or a complementary pool of cAMP that mediates LH-regulated steroidogenesis [2].
• By sequence homology in the catalytic domain, PDE9A is almost equidistant from all eight known mammalian PDE families but is most similar to PDE8A (34% amino acid identity) and least like PDE5A (28% amino acid identity) [3].
• We have isolated cDNAs encoding rat PDE8A and PDE8B from brain and testis, respectively [4].
• The PDE8A gene is revealed to contain 23 exons, and its exon-intron boundaries have been defined [5].

Biological context of PDE8A

• PDE8A is insensitive (up to 100 microM) to a variety of PDE inhibitors including rolipram, zaprinast, vinpocetine, SKF-94120, and IBMX, but is inhibited (IC50 = 9 microM) by the PDE inhibitor dipyridimole [1].
• Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution [5].

Anatomical context of PDE8A

• PDE8A is expressed in a wide variety of tissues as a approximately 4.5 kb mRNA, with highest levels in testis, ovary, small intestine, and colon [1].
• Overall, these results suggest that pharmacological manipulation of PDE8A, alone or in combination with other PDEs present in Leydig cells, may be exploited to modulate testosterone synthesis and possibly to treat various conditions where the local levels of this androgen need to be altered [2].
• Northern blot analysis indicated that the mRNA encoding PDE8B is expressed specifically and abundantly in thyroid gland as a approximately 4.2 kb mRNA, in contrast to the wide expression of PDE8A mRNA in various tissues [6].

Other interactions of PDE8A

• PDE8A is most similar to PDE4 (38.5% amino acid identity in the catalytic domain), but is clearly not a member of any of the seven known PDE families [1].
• The predicted protein sequences of PDE8B showed highest homology (65% identity, 83% similarity) to that of PDE8A [6].

Analytical, diagnostic and therapeutic context of PDE8A

• Tissue-specific expression patterns of rat PDE8A and PDE8B transcripts were demonstrated by Northern blot analysis [4].
• The sequence analysis demonstrated that rat PDE8A was a protein of 823 amino acid residues [4].

References