Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation

Molecular Pharmacology

Volumn 66, Issue 1, 2004, Pages 144-152

  Blount, Mitsi A ^a   Beasley, Alfreda ^a   Zoraghi, Roya ^a   Sekhar, Konjeti R ^a   Bessay, Emmanuel P ^a   Francis, Sharron H ^a   Corbin, Jackie D ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC GMP; PHOSPHODIESTERASE V; SILDENAFIL; TADALAFIL; TRITIUM; VARDENAFIL;

ALLOSTERISM; ANIMAL CELL; ARTICLE; BINDING SITE; CATALYSIS; COMPETITIVE INHIBITION; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; ENZYME SPECIFICITY; GENETIC HETEROGENEITY; HYDROLYSIS; NEGATIVE FEEDBACK; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; RECEPTOR AFFINITY; RECEPTOR OCCUPANCY; VASCULAR SMOOTH MUSCLE;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; BINDING SITES; CARBOLINES; CATALYTIC DOMAIN; CYCLIC GMP; HUMANS; IMIDAZOLES; KINETICS; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PIPERAZINES; PROTEIN STRUCTURE, TERTIARY; SULFONES; TRIAZINES; TRITIUM;

EID: 3042574999     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.66.1.144     Document Type: Article

References (41)

1. Aravind L and Ponting CP (1997) The GAF domain: an evolutionary link between diverse phototransducing proteins. Trends Biochem Sci 22:458-459.
2. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, and Naylor AM (1998) Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159:2164-2171.
3. Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108.
4. Chou T (1974) Relationships between inhibition constants and fractional inhibition in enzyme-catalyzed reactions with different numbers of reactants, different reaction mechanisms and different types and mechanisms of inhibition. Mol Pharmacol 10:235-247.
5. 3H]Sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous and stimulated by cGMP. Mol Pharmacol 63:1364-1372.
6. Corbin JD and Francis SH (1999) Cyclic GMP phosphodiesterase-5: target of sildenafil. J Biol Chem 274:13729-13732.
7. Corbin JD and Francis SH (2002) Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract 56:453-459.
8. Corbin JD, Francis SH, and Webb DJ (2002) Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology 60:4-11.
9. Corbin JD, Turko IV, Beasley A, and Francis SH (2000) Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. Eur J Biochem 267:2760-2767.
10. Daugan AC-M (2000), inventor, ICOS Corporation, assignee. Use of cGMP-phosphodiesterase inhibitors in methods and compositions to treat impotence. U.S. patent 6,140,329. 2000 Oct 31.
11. Francis SH, Colbran JL, McAllister-Lucas LM, and Corbin JD (1994) Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase. J Biol Chem 269:22477-22480.
12. Francis SH and Corbin JD (1988) Purification of cGMP-binding protein phosphodiesterase from rat lung, Methods Enzymol 159:722-729.
13. Francis SH, Chu DM, Thomas MK, Beasley A, Grimes K, Busch JL, Turko IV, Haik TL, and Corbin JD (1998) Ligand-induced conformational changes in cyclic nucleotide phosphodiesterases and cyclic nucleotide-dependent protein kinases. Methods 14:81-92.
14. Francis SH, Lincoln TM, and Corbin JD (1980) Characterization of a novel cGMP binding protein from rat lung. J Biol Chem 255:620-626.
15. Francis SH, Sekhar KR, Rouse AB, Grimes KA, and Corbin JD (2003) Single step isolation of sildenafil from commercially available Viagra tablets. Int J Impot Res 15:369-372.
16. Francis SH, Turko IV, and Corbin JD (2001) Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Biol 65:1-52.
17. Gopal VK, Francis SH, and Corbin JD (2001) Allosteric sites of phosphodiesterase-5 (PDE5). A potential role in negative feedback regulation of cGMP signaling in corpus cavernosum. Eur J Biochem 268:3304-3312.
18. Gresser U and Gleiter CH (2002) Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil-review of the literature. Eur J Med Res 7:435-446.
19. Laliberte F, Han Y, Govindarajan A, Giroux A, Liu S, Bobechko B, Lario P, Bartlett A, Gorseth E, Gresser M, et al. (2000) Conformational difference between PDE4 apoenzyme and holoenzyme. Biochemistry 39:6449-6458.
20. Lincoln TM, Hall CL, Park CR, and Corbin JD (1976) Guanosine 3′:5′-cyclic monophosphate binding proteins in rat tissues. Proc Natl Acad Sci USA 73:2559-2563.
21. Limbird LE (1995) Cell Surface Receptors: A Short Course on Theory and Methods, 2nd ed, Kluwer Academic Publishers, Boston.
22. Liu L, Underwood T, Li H, Pamukcu R, and Thompson WJ (2002) Specific cGMP binding by the cGMP binding domains of cGMP-binding cGMP specific phosphodiesterase. Cell Signal 14:45-51.
23. Manganiello VC, Smith CJ, Degerman E, and Belfrage P (1990) Cyclic GMP-inhibited cyclic nucleotide phosphodiesterases, in Cyclic Nucleotide Phosphodiesterases: Structure, Regulation and Drug Action (Beavo J and Houslay M eds) pp 87-109, John Wiley and Sons, New York.
24. Martins TJ, Mumby MC, and Beavo JA (1982) Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from bovine tissues. J Biol Chem 257:1973-1979.
25. McAllister-Lucas LM, Sonnenburg WK, Kadlecek A, Seger D, LeTrong H, Colbran JL, Thomas MK, Walsh KA, Francis SH, Corbin JD, et al. (1993) The structure of a bovine lung cGMP-binding, cGMP-specific phosphodiesterase deduced from a cDNA clone. J Biol Chem 268:22863-22873.
26. Mullershausen F, Friebe A, Feil R, Thompson WJ, Hofmann F, and Koesling D (2003) Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling. J Cell Biol 160:719-727.
27. Mullershausen F, Russwurm M, Thompson WJ, Liu L, Koesling D, and Friebe A (2001) Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5 paralleled by phosphorylation of the enzyme. J Cell Biol 155:271-278.
28. Murthy KS (2001) Activation of phosphodiesterase 5 and inhibition of guanylate cyclase by cGMP-dependent protein kinase in smooth muscle. Biochem J 360:199-208.
29. Okada D and Asakawa S (2002) Allosteric activation of cGMP-specific, cGMP-binding phosphodiesterase (PDE5) by cGMP. Biochemistry 41:9672-9679.
30. Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, and Beavo JA (2002) Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem 277:3310-3317.
31. Rybalkin SD, Rybalkina IG, Shimizu-Albergine M, Tang XB, and Beavo JA (2003) PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO (Eur Mol Biol Organ) J 22:469-478.
32. Saenz de Tejada I, Angulo J, Cuevas P, Fernandez A, Moncada I, Allona A, Lledo E, Korschen HG, Niewohner U, Haning H, et al. (2001) The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res 13:282-290.
33. Schneider HH, Schmiechen R, Brezinski M, and Seidler J (1986) Stereospecific binding of the antidepressant rolipram to brain protein structures. Eur J Pharmacol 127:105-115.
34. Shimizu-Albergine M, Rybalkin SD, Rybalkina IG, Feil R, Wolfsgruber W, Hofmann F, and Beavo JA (2003) Individual cerebellar Purkinje cells express different cGMP phosphodiesterases (PDEs): in vivo phosphorylation of cGMP-specific PDE (PDE5) as an indicator of cGMP-dependent protein kinase (PKG) activation. J Neurosci 23:6452-6459.
35. Sung BJ, Yeon Hwang K, Ho Jeon Y, Lee JI, Heo YS, Hwan Kim J, Moon J, Min Yoon J, Hyun YL, Kim E, et al. (2003) Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature (Lond) 425:98-102.
36. Thomas MK, Francis SH, and Corbin JD (1990a) Characterization of a purified bovine lung cGMP-binding cGMP phosphodiesterase. J Biol Chem 265:14964-14970.
37. Thomas MK, Francis SH, and Corbin JD (1990b) Substrate- and kinase-directed regulation of phosphorylation of a cGMP-binding phosphodiesterase by cGMP. J Biol Chem 255:14971-14978.
38. Torphy TJ, Livi GP, Balcarek JM, White JR, Chilton FH, and Undem BJ (1992) Therapeutic potential of isozyme-selective phosphodiesterase inhibitors in the treatment of asthma. Adv Second Messenger Phosphoprotein Res 25:289-305.
39. Turko IV, Ballard SA, Francis SH, and Corbin JD (1999) Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. Mol Pharmacol 56:124-130.
40. Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, and Zapol WM (2000) Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology 92:1702-1712.
41. Wyatt TA, Naftilan AJ, Francis SH, and Corbin JD (1998) ANF elicits phosphorylation of the cGMP phosphodiesterase in vascular smooth muscle cells. Am J Physiol 274:H448-H455.