Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases.
Type III cGMP-inhibited phosphodiesterases (PDE3s) play important roles in hormonal regulation of lipolysis, platelet aggregation, myocardial contractility, and smooth muscle relaxation. We have recently characterized two PDE3 subtypes (PDE3A and PDE3B) as products of distinct but related genes. To elucidate their biological roles, in this study we compare cellular patterns of gene expression for these two enzymes during rat embryonic and postnatal development using in situ hybridization. PDE3B [corrected] mRNA is abundant in adipose tissue and is also expressed in hepatocytes throughout development. This mRNA is also highly abundant in embryonic neuroepithelium including the neural retina, but expression is greatly reduced in the mature nervous system. Finally, PDE3B [corrected] mRNA is localized in spermatocytes and renal collecting duct epithelium in adult rats. PDE3B mRNA is highly expressed in the cardiovascular system, including myocardium and arterial and venous smooth muscle, throughout development. It is also abundant in bronchial, genitourinary and gastrointestinal smooth muscle and epithelium, megakaryocytes, and oocytes. PDE3A [corrected] mRNA demonstrates a complex, developmentally regulated pattern of gene expression in the central nervous system. In summary, the two different PDE3s show distinctive tissue-specific patterns of gene expression suggesting that PDE3B [corrected] is involved in hormonal regulation of lipolysis and glycogenolysis, while regulation of myocardial and smooth muscle contractility appears to be a function of PDE3A [corrected]. In addition, the present findings suggest previously unsuspected roles for these enzymes in gametogenesis and neural development.
Reinhardt
R R
RR
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Chin
E
E
Zhou
J
J
Taira
M
M
Murata
T
T
Manganiello
V C
VC
Bondy
C A
CA
D000818:Animals; D001483:Base Sequence; D006152:Cyclic GMP / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D015870:Gene Expression; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000302:isolation & purification*; D051381:Rats; D014018:Tissue Distribution
D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP