Adrenergic Contraction of Human Prostate Tissues Is Maintained Under the Rab GTPase Inhibitors Nexhinib20 and CID1067700

ABSTRACT α 1 ‐Adrenoceptors are an important drug target in benign prostatic hyperplasia (BPH) and have been intensively studied at the expression level, but their posttranslational regulation in the prostate is widely unknown. Here we examined modulation of prostate smooth muscle contractions by inhibitors for RabGTPases, which are involved in intracellular transport of internalized receptors and in vesicle function. Tissues were obtained from laser enucleation for BPH and from radical prostatectomy without prior BPH surgery. Contractions were induced in an organ bath, with and without the Rab27 inhibitor nexhinib20 or the Rab7 inhibitor CID1067700. Nexhinib20 reduced contractions induced by electric field stimulation (EFS) at 10 μM in laser‐enucleated tissues ( E max 79% [34–125] of KCl‐induced contraction in controls, 40% [6–74] of KCl with nexhinib20, p = 0.0234), but not at 1 μM or in prostatectomized tissues. Contractions by phenylephrine, methoxamine and noradrenaline were resistant to consistent modulation by nexhinib20 and CID1067700, both at 1 μM and 10 μM and in both types of prostate tissues. EFS‐induced contractions of laser‐enucleated and prostatectomized tissues remained unaltered with CID1067700. The lack of consistent effects of CID1067700 despite previously reported Rab7‐dependent regulation of α 1A ‐adrenoceptors questions the transferability of findings from receptor overexpression systems and biochemical small GTPase assays to endogenous receptor regulation in human tissues. Divergent responsiveness of neurogenic and agonist‐induced contractions to nexhinib20 and CID1067700 suggests Rab7‐independent regulation of α 1 ‐adrenoceptor‐mediated contraction, but a possible presynaptic role of Rab27 in neurotransmission of human prostate smooth muscle.