![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
R Alvarez, GL Banerjee, JJ Bruno, GL Jones, K Littschwager, AM Strosberg and MC Venuti
Some biochemical and pharmacological properties of a novel, potent inhibitor of cyclic AMP phosphodiesterase, N-cyclohexyl-N-methyl-4-(7- oxy-1,2,3,5-tetrahydroimidazo[2,1-b] quinazolin-2-one) butyramide (RS- 82856), were investigated. RS-82856 selectively inhibits the high affinity form of cyclic AMP phosphodiesterase (type IV) isolated from human platelets (Ki = 0.5 nM) with only weak effects on both the nonspecific and cyclic GMP-sensitive phosphodiesterases. The inhibitor reduces both maximum velocity and substrate affinity of the type IV enzyme. This mixed pattern of partial competitive and noncompetitive inhibition was also obtained with one of the two high affinity forms of phosphodiesterase found in dog heart (Ki = 0.75 nM). Of several human and dog tissues examined, RS-82856 exhibits marked selectively for the platelet high affinity enzyme. It also has significant inhibitory effects on cardiac membrane-bound phosphodiesterase. RS-82856 inhibits the aggregation of human platelets in response to adenosine 5'- diphosphate (IC50 = 0.11 microM) in vitro and is active ex vivo for at least 2 hr following oral administration (10 mg/kg) to rhesus monkeys. Administration of RS-82856 to instrumented, anesthetized dogs by either intravenous or intraduodenal routes increases cardiac contractile force and reduces afterload. These data suggest that RS-82856 may be useful as an agent to increase cardiac output in the treatment of congestive heart failure.
This article has been cited by other articles:
|
|
 |
|
  J. Cheng, M. A. Thompson, H. J. Walker, C. E. Gray, M. M. Diaz Encarnacion, G. M. Warner, and J. P. Grande Differential regulation of mesangial cell mitogenesis by cAMP phosphodiesterase isozymes 3 and 4 Am J Physiol Renal Physiol, November 1, 2004; 287(5): F940 - F953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gonzalez-Serratos, R. Chang, E. F. R. Pereira, N. G. Castro, Y. Aracava, P. A. Melo, P. C. Lima, C. A. M. Fraga, E. J. Barreiro, and E. X. Albuquerque A Novel Thienylhydrazone, (2-Thienylidene)3,4-methylenedioxybenzoylhydrazine, Increases Inotropism and Decreases Fatigue of Skeletal Muscle J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 558 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C.S. Chini, J. P. Grande, E. N. Chini, and T. P. Dousa Compartmentalization of cAMP Signaling in Mesangial Cells by Phosphodiesterase Isozymes PDE3 and PDE4. REGULATION OF SUPEROXIDATION AND MITOGENESIS J. Biol. Chem., April 11, 1997; 272(15): 9854 - 9859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Degerman, P. Belfrage, and V. C. Manganiello Structure, Localization, and Regulation of cGMP-inhibited Phosphodiesterase (PDE3) J. Biol. Chem., March 14, 1997; 272(11): 6823 - 6826. [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
