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Pharmacological characterization of isolated human prostate
Robert R Kester1, Unni M Mooppan, Angelo E Gousse
1Departments of Urology and Anesthesiology, Brookdale University Medical Center, Brooklyn, NY, USA.
The Journal of Urology
|August 13, 2003
Summary
Human prostate contains alpha-1 adrenergic, cholinergic, and nonadrenergic noncholinergic neuroreceptors. Drug interactions suggest potential for new benign prostatic hyperplasia treatments.
Area of Science:
- Pharmacology
- Urology
- Neuroscience
Background:
- The human prostate possesses alpha-1 adrenergic, cholinergic, and nonadrenergic noncholinergic neuroreceptors.
- Understanding these receptors is crucial for managing conditions like benign prostatic hyperplasia (BPH).
Purpose of the Study:
- To investigate the contractile responses in isolated human prostate tissue using agonistic and antagonistic agents targeting specific neuroreceptors.
- To characterize the neuroreceptor profile of the human prostate.
Main Methods:
- Human prostate tissue samples were obtained from 37 patients undergoing prostatectomy for BPH.
- Tissue specimens were suspended in a tissue bath and subjected to agonist-induced contractions, with norepinephrine (NE) as the initial agonist.
- Tissues were pretreated with various antagonists (adrenergic, cholinergic, nonadrenergic noncholinergic) before exposure to a second agonist, and contractile tensions were recorded and analyzed.
Main Results:
- Norepinephrine (NE) induced the strongest contractile force, followed by dopamine, acetylcholine, bethanechol, histamine, and serotonin.
- Specific alpha-1 adrenergic receptor blockers, including terazosin, prazosin, and LY253352, showed significant differences in antagonism.
- The order of alpha-1 adrenergic antagonistic strength was LY253352 > prazosin > terazosin > ketanserin > SCH23390 > diphenhydramine > DO710 > dopamine > serotonin > histamine.
Conclusions:
- Human prostate neuroreceptors include alpha-1 adrenergic, dopaminergic, muscarinic cholinergic, 2A serotonergic, and H1 histaminergic types.
- Interactions between dopamine, serotonin, histamine, and their antagonists suggest potential receptor-receptor cross-talk within the prostate.
- Further pharmacological research may lead to novel drug development for treating bladder outlet obstruction in BPH patients.