Transient Receptor Potential Al and Cannabinoid Receptor Activity in Human Normal and Hyperplastic Prostate: Relation to Nerves and Interstitial Cells

摘要

Background: Ion channel transient receptor potential Al (TRPA1) and cannabinoid (CB) receptors are involved in mechanoafferent signaling from the bladder and the urethra. Objective: To characterize TRPA1-, CB1-, and CB2-receptor activities in the human prostate. Design, setting, and participants: Prostate specimens were obtained from 12 patients undergoing radical prostatectomy. We studied expressions (n = 6) of TRPA1, CB1, and CB2 receptors and effects of the TRPA1 agonists allyl isothiocyanate (A1), cinnamalde-hyde (CA), sodium hydrogen sulfide (NaHS), and CP 55940 (a CB1/CB2 agonist) on prostatic preparations. Measurements: Western blot, immunohistochemistry, and functional experiments were performed. Results and limitations: Western blot detected expected bands for CB1, CB2, and TRPA1. TRPA1 immunoreactivity was located on nerves that were positive for CB1, CB2, calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), or vesicular acetylcholine transporter (VAChT). CB1 and CB2 immunoreactivity was found on nerves that were positive for NOS, VAChT, or CGRP. Adrenergic nerves were not immunoreactive for TRPA1, CB1, or CB2. In nodular hyperplasia, nerves containing the above markers were scarce or absent. TRPA1 immunoreactivity was detected in cyclic guanosine monophosphate-posi-tive basal cells of the glandular epithelium. Basal or subepithelial TRPA1-immunoreactive cells contained vimentin and c-kit immunoreactivity. CA and NaHS relaxed precontracted preparations by 55 ? 7% and 35 ? 3% (n = 6 for each). CP 55940, NaHS, A1, capsaicin, and CA decreased nerve contractions up to 27%, 80%, 47%, and 87%, respectively (n = 6 for each). Conclusions: The distribution and function of TRPA1 and CB receptors in prostatic tissue suggest a role for these receptors in mechanoafferent signals, epithelial homeostasis, emission, or inflammation of the human prostate.