Endothelin-1 production and agonist activities in cultured prostate-derived cells: Implications for regulation of endothelin bioactivity and bioavailability in prostatic hyperplasia
✍ Scribed by Walden, Paul D.; Ittmann, Michael; Monaco, Marie E.; Lepor, Herbert
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 205 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0270-4137
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✦ Synopsis
Background:
Endothelin-1 (et-1) interacts with specific g-protein-coupled receptors to initiate short-term (contraction) and long-term (mitogenesis) events in target cells. et-1 is an abundant prostate secretory protein that, in its biologically active form, elicits prostatic smooth muscle contraction. the present study was designed to determine the effects of et-1 on prostate cell growth and to examine the regulation of endogenous et-1 activity and bioavailability.
Methods:
Primary cultures of prostate secretory epithelial (pe) and prostate fibromuscular stromal (ps) cells were established from benign human prostate tissue.
Results:
In culture, pe cells secrete immunoreactive et-1 (38.5 +/- 1.6 pg/ml/10(6) cells/24 hr) into the conditioned medium. levels of immunoreactive et-1 produced by ps cells were more than 10-fold lower. endothelin-converting enzyme-1 (ece-1) mrna was detected in pe cells and not in ps cells; however, big et-1 was the predominant immunoreactive et-1 secretory product of pe cells. the et(b) endothelin receptor was the predominant subtype in both pe and ps cells. in ps cells, but not pe cells, et-1 induced significant inositol phosphate accumulation and [3h]-thymidine uptake. agonist activity was inhibited by the et(b) receptor selective antagonist, bq 788. intact pe cell monolayers secrete et-1 through the apical surface, consistent with secretion of et-1 into the glandular lumen in vivo.
Conclusions:
On the basis of these findings, regulation of et-1 activity and bioavailability appears to be tightly regulated. such findings have important implications in the pathophysiology of prostate disease.