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Pharmacological characterization of the isolated canine prostate
1Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Pharmacology, Princeton, New Jersey, USA.
Purpose:
The goal of the present study was to characterize the responses of the isolated normal canine prostate to various contracting and relaxing stimuli to determine which pharmacological agents may have utility against the dynamic component of benign prostatic hyperplasia (BPH).
Materials And Methods:
Isometric force development was measured in isolated strips of prostate tissue.
Results:
The alpha-adrenergic agonists were the most efficacious stimulants tested (phenylephrine EC50=2.1 microM.). Endothelin-1, acting primarily via ETA receptors, was more potent (EC50=27nM.) but less efficacious. Histamine (EC50=14.7 microM.), serotonin (EC50=0.12 microM.), carbachol (EC50=5.9 microM.) and KC1 (EC50=48.8 mM.) were also less efficacious than phenylephrine. Nifedipine was a potent (IC50=28 nM.) and efficacious (74% inhibition) inhibitor of phenylephrine-induced force. Potassium channel activator drugs were also efficacious relaxants, producing approximately 80% inhibition of force; rank order of potency was P1075 > cromakalim > diazoxide. Sodium nitroprusside was a weak relaxant, producing only approximately 40% relaxation at a concentration of 100 micronM. Both isoproterenol and forskolin were effective relaxants (75 to 90% relaxation).
Conclusions:
We conclude that potassium channel activators, adenylate cyclase stimulators, or endothelin antagonists may have utility against the dynamic component of outflow obstruction secondary to BPH.