Biology Reference
In-Depth Information
antidepressant-like effects in some animal models of depression (Liebenberg et al.
2010
). However, further studies on the potential antidepressant-like effect of PDE5
inhibitors are needed.
3.6 PDE6
PDE6 expression is confined to the retina and pineal in some species and its
inhibition is not directly relevant to psychopharmacology.
3.7 PDE7
The PDE7 gene family consists of two genes, PDE7A and PDE7B, with high
affinity for cAMP, determined by its targeting domain at the N-terminal. Three
splice variants of PDE7A are identified in humans, PDE7A1, PDE7A2, and
PDE7A3, which differ in their N- and C-terminal regions (Han et al.
1997
); the
PDE7A1 promoter contains a cAMP-responsive element (Torras-Llort and Azorin
2003
). Besides its wide expression in the CNS, PDE7 mRNA and protein are also
expressed in immune and proinflammatory cells. Some investigators have sug-
gested that PDE7A may play a role in both activation and proliferation of T cells
and in the regulation of human B-lymphocytes (Li et al.
1999
; Lee et al.
2002
;
Kadoshima-Yamaoka et al.
2009
), although some studies have questioned the
importance of this enzyme in T-cell function (Smith et al.
2004
; Yang et al.
2003
; Guo et al.
2009
). Altered immune and CNS interactions have been implicated
in depression (Mendelovic et al.
1997
,
1999
), suggesting that PDE7 inhibition may
affect mood by multiple mechanisms.
The highest levels of PDE7A mRNA expression are found in the hippocampus
and olfactory bulb (Miro et al.
2001
). Some overlap of the expression pattern can be
observed when PDE7A mRNA localization is compared with that of the other
cAMP-specific PDEs such as the PDE4 family (Miro et al.
2001
;P
ยด
rez-Torres et al.
2001
). The consistent colocalization with PDE4 mRNAs supports the hypothesis
that PDE7A could have effects on memory impairment and depression. Previous
studies demonstrated the cAMP/PKA/CREB pathway-mediated transcriptional acti-
vation of PDE7B is through the dopamine D1 receptor in primary striatal cultures
(Reyes-Irisarri et al.
2005
). Sasaki et al. (
2004
) examined the regional distribution
and cellular localization of PDE7B mRNA in rat brain by in situ hybridization
histochemistry. They found that 74 and 79% of the cells expressing PDE7B mRNA
in striatum and olfactory tubercle are GABAergic cells (expressing glutamic acid
decarboxylase mRNA). Although the role of PDE7B in vivo remains unclear, these
results offer a neuroanatomical and neurochemical basis that supports the search for
specific functions for the development of specific PDE7 inhibitors (Reyes-Irisarri
et al.
2005
).
