Evaluating the significance of cyclic adenosine monophosphate-mediated signaling in human prostate: a functional and biochemical study.
OBJECTIVE
To investigate further the potential significance of the cyclic adenosine monophosphate (cAMP) pathway in the control of prostate smooth muscle. The cAMP pathway has been assumed to be an alternative pharmacologic target to treat dysfunctions of the human lower urinary tract. To date, only a few studies have addressed the physiologic relevance of cAMP signal transduction in the control of human prostate function.


METHODS
Phosphodiesterase activity was isolated from microsomal fractions prepared from prostatic tissue and subjected to biochemical analysis. Using the organ bath technique, the effects of the phosphodiesterase type (PDE)4 inhibitors Ro 20-1724, rolipram, and RP 73401 on the tension induced by norepinephrine of isolated prostatic tissue were investigated and compared with the PDE5 inhibitor sildenafil and BAY 13-1197, a nitric oxide-independent activator of the soluble guanylyl cyclase. Statistical analysis was conducted using the Gosset t test.


RESULTS
Biochemical analysis of the microsomal fraction revealed only a single peak of PDE activity that was sensitive to papaverine and the PDE4 inhibitors rolipram and Ro 20-1724. The tension induced by norepinephrine was reversed by the drugs with the following order of efficacy: Ro 20-1724, RP 73401, rolipram, sildenafil, and BAY 13-1197. Pre-exposure of the tissue to a threshold concentration (0.05 μM) of forskolin (adenlyl cyclase activator) increased the reversion of tension induced by rolipram and RP 73401 and the PDE5 inhibitor sildenafil.


CONCLUSIONS
These results have provided evidence for the significance of cAMP signaling in the control of prostate smooth muscle.
Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany. sue_de_99@yahoo.de
George T
GT
Kedia
Stefan
S
Ückert
Hamiyet
H
Polat
Axel S
AS
Merseburger
Markus A
MA
Kuczyk
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000368:Aged; D001549:Benzamides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology
D001549:Benzamides; D058988:Phosphodiesterase 4 Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011725:Pyridines; D013450:Sulfones; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000068677:Sildenafil Citrate; D010208:Papaverine; D000242:Cyclic AMP; D020889:Rolipram; C087566:piclamilast