Expression and regulation of human and rat phosphodiesterase type IV isogenes

Abstract

Type IV phosphodiesterases (PDE IV) specifically hydrolyze cAMP and are inhibited by rolipram. RT-PCR was applied to analyze the expression patterns of mRNAs for four cloned human and rat phosphodiesterase type IV isogenes (PDE IV-A, -B, -C and -D). Although these patterns were mostly coincident for the human and rat PDE IV genes, some differences were found between the two species. PDE IV-A expression was detectable in human blood but not in rat blood, suggesting a species-specific difference in the expression of this PDE IV isogene. PDE IV-C was neither detected in human or rat blood nor in different cell populations of the human immune system. It is further demonstrated that the PDE IV isogene expression is differentially regulated by cAMP in different cell types.

Identification of cyclic AMP‐phosphodiesterase variants from the PDE4D gene expressed in human peripheral mononuclear cells

“…In contrast to our results, a previous study has shown that in a human leukemic lymphocyte line expression of PDE4D3 mRNA could only be detected after dibutyryl cAMP treatment of the cells [40]. The presence of variants PDE4D1 and PDE4D2 was not addressed.…”

“…Previous studies on promonocytic cell lines pointed to the expression of PDE4D3 in unstimulated U937 cells [31,37,40], and to its absence in Mono Mac 6 cells [38]. The expression of other isoforms, namely PDE4D1, PDE4B2, and PDE4A5, was induced by cAMP-elevating agents in these cell lines [37,38,40].…”

“…Previous studies on promonocytic cell lines pointed to the expression of PDE4D3 in unstimulated U937 cells [31,37,40], and to its absence in Mono Mac 6 cells [38]. The expression of other isoforms, namely PDE4D1, PDE4B2, and PDE4A5, was induced by cAMP-elevating agents in these cell lines [37,38,40]. Thus, there remains considerable uncertainty concerning the forms expressed in unstimulated normal human monocytes, and it is difficult to completely rule out the participation of this cell type to the isoenzyme expression pattern we have determined from blood mononuclear cells.…”

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L‐type Ca2+ current in rat ventricular myocytes

“…Cyclic nucleotide PDEs exist in multiple molecular forms (Stoclet et al, 1995;Loughney & Ferguson, 1996) and at least four di erent subtypes have been shown to coexist in the heart muscle Bode et al, 1991;Dubois et al, 1993;Taira et al, 1993;Engels et al, 1994;Kostic et al 1997): (1) a Ca 2+ /calmodulin-activated PDE (PDE1) which hydrolyzes cyclic AMP and cyclic GMP; (2) a cyclic GMPstimulated PDE (PDE2) which hydrolyzes cyclic AMP and cyclic GMP; (3) a cyclic GMP-inhibited PDE (PDE3) which hydrolyzes cyclic AMP with high a nity (low K m ) and (4) and a cyclic GMP-independent PDE (PDE4) which hydrolyzes selectively cyclic AMP with high a nity. All these PDEs can be inhibited by xanthine derivatives, such as 3-isobutyl-1-metylxanthine (IBMX) or ca eine, which have been frequently used to evaluate the role of PDEs in the metabolism of cyclic AMP in cardiac preparations (see e.g.…”

Expression of mRNA encoding cAMP‐specific phosphodiesterase isoforms in rat parotid glands

“…An intense band of PDE4D was observed, while the band for PDE4C was weak. Further investigation compared the expressions of the PDE4 subfamily in the rat parotid with those in the rat brain, testis, in which PDE4A, PDE4B, PDE4C and PDE4D have been already characterized (14,24), and pancreatic glands (Fig. 3).…”