Journal Article

Purinergic smooth muscle contractions in the human prostate: estimation of relevance and characterization of different agonists

Annabel Spek, Ru Huang, Yuhan Liu, Bingsheng Li, Ruixiao Wang, Raphaela Waidelich, Martin Hennenberg, Frank Strittmatter, Beata Rutz, Christian G. Stief, Anna Ciotkowska

2021

Overview

Non-adrenergic prostate smooth muscle contractions may account for the limited effectiveness of α 1 -adrenoceptor antagonists, which are the first-line option for medical treatment of voiding symptoms suggestive of benign prostatic hyperplasia. In non-human prostates, purinergic agonists induce contractions reaching similar magnitudes as α 1 -adrenergic contractions. However, evidence for the human prostate is highly limited, and pointed to much weaker purinergic contractions. Here, we examined contractions of different purinergic agonists in human prostate tissues. Tissues were obtained from radical prostatectomy. Contractions were studied in an organ bath, and expression of purinergic receptors was studied by RT-PCR. Electric field stimulation (EFS)–induced contractions amounted to 104% of KCl-induced contractions (95% CI: 84–124%). From all tested agonists, only ATP induced concentration-dependent contractions, reaching an average maximum of 18% (12–24%) of KCl. Maximum tensions following application of other agonists averaged to 7.1% of KCl for α,β-methylene-ATP (1.8–12.4%), 3.9% for β,γ-methylene-ATP (2.0–5.4%), 3.1% for 2-methylthio-ATP (− 0.1–6.3%), and 5.1% for ATPγS (1.0–9.2%). Responses were not affected by the P2X antagonist NF023 or the P2Y antagonist PPADS. mRNA expression of P2X1-4 correlated with expression of a marker for catecholaminergic nerves, although neither ATP, NF023, nor PPADS changed EFS-induced contractions. Correlation between expression of receptors and the smooth muscle marker calponin was not observed. Our findings point to a low relevance of purinergic contractions in the human prostate, compared to other contractile stimuli in the human prostate and compared to purinergic contractions in non-human prostates. Purinergic contractions in the human prostate are not sensitive to NF023 or PPADS.

• Publisher: Springer Science and Business Media LLC,Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adrenergic receptors / Agonists / Animals / Biomedical and Life Sciences / Biomedicine / Calponin / Dose-Response Relationship, Drug / Dose-Response Relationship, Drug [MeSH] ; Swine [MeSH] ; Prostate/drug effects [MeSH] ; Purinergic Agonists/administration ; Reverse Transcriptase Polymerase Chain Reaction [MeSH] ; Humans [MeSH] ; Receptors, Purinergic/drug effects [MeSH] ; Muscle, Smooth/drug effects [MeSH] ; Receptors, Purinergic/metabolism [MeSH] ; Animals [MeSH] ; Smooth muscle contraction ; Electric Stimulation [MeSH] ; Original Article ; Purinergic Agonists/pharmacology [MeSH] ; Purinergic receptors ; Male [MeSH] ; Prostate/metabolism [MeSH] ; P2Y ; Muscle, Smooth/metabolism [MeSH] ; Muscle Contraction/drug effects [MeSH] ; P2X ; Benign prostatic hyperplasia (BPH) ; Lower urinary tract symptoms (LUTS) ; Species Specificity [MeSH] / Electric Stimulation / Gene expression / Humans / Hyperplasia / Male / Medical treatment / Muscle Contraction / Muscle Contraction - drug effects / Muscle, Smooth / Muscle, Smooth - drug effects / Muscle, Smooth - metabolism / Nerves / Neurosciences / Original / Original Article / Pharmacology/Toxicology / Polymerase chain reaction / Potassium chloride / Prostate / Prostate - drug effects / Prostate - metabolism / Prostatectomy / Purine P2X receptors / Purine P2Y receptors / Purine receptors / Purinergic Agonists / Purinergic Agonists - administration & dosage / Purinergic Agonists - pharmacology / Receptors, Purinergic / Receptors, Purinergic - drug effects / Receptors, Purinergic - metabolism / Reverse Transcriptase Polymerase Chain Reaction / Smooth muscle / Species Specificity / Swine / Urological surgery