Biology Reference
In-Depth Information
Fig. 2 Antagonistic effects of the guanylyl cyclase inhibitor ODQ (20 mg/kg) on the anxiolytic
effects of Bay 60-7550 (Bay) in the elevated plus-maze (a, b) and both Bay 60-7550 and ND7001
in the hole-board tests (c and d). Values are expressed as means
6-8).
#
p
SEM (
n
ΒΌ
0.05;
<
##
p
0.01 compared to control;
*
p
0.05;
**
p
0.01 compared to Bay 60-7550 and ND7001.
Doses shown parenthetically are mg/kg, i.p. Reprinted with permission from (Masood et al.
2009
)
<
<
<
3.4 PDE4
PDE4 consists of a large family of isoforms encoded by four genes that specifically
hydrolyze cAMP with high affinity and are not sensitive to either cGMP or Ca
2+
/
calmodulin (Conti et al.
2003
; Houslay et al.
2007
; Houslay
2010
). Individual
isoforms are thought to have specific functional roles in cells by virtue of associa-
tion with partner proteins that target them to functionally relevant sites in the cell
(Houslay
2010
).
Interest linking PDE4 to cognitive effects stemmed from the pioneering work of
Wachtel (
1982
), who described the discovery of a selective PDE4 inhibitor roli-
pram and its antidepressant effects. PDE4 has since been implicated in various
disorders such as depression, anxiety, and inflammation-related disorders (Barnette
and Underwood
2000
; Houslay
2001
; Houslay et al.
2005
; O'Donnell and Zhang
2004
; Zhang
2009
). Recent studies have extended the therapeutic potential of PDE4
