ABSTRAK Niluh. Tantri 2011.Phosphodiesterase Inhibitor.

Tinjauan Kepustakaan, Program Pendidikan Dokter Spesialis I Ilmu Penyakit Paru Fakultas Kedokteran Universitas Brawijaya Malang. Pembimbing : dr.Susanthy Djajalaksana, SpP(K). Sejak ditemukannya cAMP sebagai second messenger, penelitian tentang tranduksi sinyal antar sel dan cara kerja hormon terbuka lebar. Cyclics nucletotides memiliki peran yang sangat penting dalam proses kerja hormon. Hormon berikatan dengan reseptor yang diperantarai oleh protein G terhadap enzym cyclase, yang kemudian mensintesis cAMP/cGMP. Dalam daur cAMP, fosfodiesterase (PDE) adalah enzim yang menghidrolisis cAMP dan cGMP, yang berarti menginaktivasi second messenger. Bersama-sama dengan fosfatase, PDE adalah feedback negatif dalam jaras sinyal kerja hormon, dan fungsi enzim ini adalah menghentikan transmisi sinyal. Tetapi, bila dilihat proses komunikasi intraseluler secara keseluruhan, maka enzim fosfodiesterase ternyata memiliki peran yang lebih besar dalam jaras sinyal. Saat ini telah ditemukan setidaknya 11 golongan phospodiesterase inhibitor, yang masing masing memiliki memiliki spesitifitas substrat, kinetik, allosteric regulation dan lokasi subselular yang berbeda. Penggunaan PDE sebagai target terapi dalam penyakit paru telah banyak berkembang, yang sedang marak diteliti adalah penggunaan PDE4 inhibitor dan PDE5 inhibitor, PDE4 inhibitor diketahui memiliki efek antiinflamasi yang memegang peranan penting dalam patofisiologi COPD, sedangkan PDE5 inhibitor sedang diteliti penggunaannya dalam hipertensi pulmonal. Kata kunci : cAMP, Phospodiesterase Inhibitor, COPD, Hipertensi Pulmonal.

ABSTRACT Niluh. Tantri 2011. Phosphodiesterase Inhibitor, Review Article. Program Pendidikan Dokter Spesialis I Pulmonology Department. Faculty of Medicine Brawijaya University. Supervisor : Dr. Susanthy Djajalaksana, SpP(K). Since the discovery of cAMP as second messengers,i research on signal transduction between cells and the way hormones work is wide open. Cyclics nucletotides have a very important role in the work process hormones. The hormone binds to receptors mediated by G proteins of the cyclase enzyme, which synthesizes cAMP / cGMP. In the cycle of cAMP, phosphodiesterase (PDE) are enzymes that hydrolyze cAMP and cGMP, which means that inactivates the second messenger. Together with phosphatase, PDE is a negative feedback signal pathways work in hormones, and this enzyme function is to stop the transmission of signals. However, when viewed intracellular communication process as a whole, then the enzyme phosphodiesterase appeared to have a greater role in signaling pathways. It has been found at least 11 classes phospodiesterase inhibitors, which each have a spesific substrate, kinetic, allosteric regulation and different subcellular locations. The use of PDE as a therapeutic target in lung disease has been widely developed, the most emerging research is the use of PDE4 inhibitors and PDE5 inhibitors. PDE4 inhibitors are known to have anti-inflammatory effect which plays an important role in the pathophysiology of COPD, whereas the PDE5 inhibitor being investigated its use in pulmonary hypertension. Key words : cAMP, Phospodiesterase Inhibitor, COPD, Pulmonary hypertension.