SMOOTH-MUSCLE CONTRACTILITY IN PROSTATIC HYPERPLASIA - ROLE OF CYCLICADENOSINE-MONOPHOSPHATE

The role of cyclic 3'-5' adenosine monophosphate (cAMP) on alpha(1)-ad renoceptor alpha(1)-receptor) induced smooth muscle contractions in sy mptomatic benign prostatic hyperplasia (BPH) was investigated. Applica tion of the selective alpha(1)-receptor agonist phenylephrine (PE) ind uced fully reversible contractions in a dose-dependent fashion. Phosph odiesterase (PDE) inhibitors blocking the degradation of cAMP suppress ed the PE induced contractions as follows: theophylline (1 mM), 91.1 /- 1.4%; papaverine (0.5 mM), 822.8 +/- 3.2%; milrinone (0.5 mM), 68.2 +/- 0.6%. Forskolin (50 mu M), which elevates cAMP through direct act ivation of adenylatecyclase (AC), inhibited the PE induced contraction s by 82.4 +/- 3.6%. To further increase the intracellular cAMP concent ration ([cAMP](i)), the membrane permeable cAMP analogue N-6-2'-O-dibu tyryladenosine derivative (dBcAMP; 1 mM) was applied and reduced the P E evoked contractions by 69.8 +/- 2.3%. We conclude that elevation of [cAMP](i) is an important step in inducing smooth muscle relaxation. ( C) 1994 Wiley-Liss, Inc.