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.
Drescher
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Urology Section, VA Hospital, Madison, WI 53705.
Eckert
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Madsen
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PO
D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D020105:Milrinone; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D010208:Papaverine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011470:Prostatic Hyperplasia / Q000503:physiopathology*; D011728:Pyridones / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D011728:Pyridones; D005576:Colforsin; D010656:Phenylephrine; D003994:Bucladesine; D013806:Theophylline; D010208:Papaverine; D000242:Cyclic AMP; D020105:Milrinone