Smooth muscle contractility in prostatic hyperplasia: role of cyclic adenosine monophosphate

The role of cyclic 3'-5' adenosine monophosphate (cAMP) on alpha 1-adrenoceptor (alpha 1-receptor) induced smooth muscle contractions in symptomatic benign prostatic hyperplasia (BPH) was investigated. Application of the selective alpha 1-receptor agonist phenylephrine (PE) induced fully reversible contractions in a dose-dependent fashion. Phosphodiesterase (PDE) inhibitors blocking the degradation of cAMP suppressed 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 microM), which elevates cAMP through direct activation of adenylatecyclase (AC), inhibited the PE induced contractions by 82.4 +/- 3.6%. To further increase the intracellular cAMP concentration ([cAMP]i), the membrane permeable cAMP analogue N6-2'-O-dibutyryladenosine derivative (dBcAMP; 1 mM) was applied and reduced the PE evoked contractions by 69.8 +/- 2.3%. We conclude that elevation of [cAMP]i is an important step in inducing smooth muscle relaxation.