Selective inhibition of neurogenic, but not agonist-induced contractions by phospholipase A2 inhibitors points to presynaptic phospholipase A2 functions in contractile neurotransmission to human prostate smooth muscle

Abstract

Background: Phospholipases A₂ (PLA₂ ) may be involved in α₁ -adrenergic contraction by formation of thromboxane A₂ in different smooth muscle types. However, whether this mechanism occurs with α₁ -adrenergic contractions of the prostate, is still unknown. While α₁ -adrenoceptor antagonists are the first line option for medical treatment of voiding symptoms in benign prostatic hyperplasia (BPH), improvements are limited, probably by nonadrenergic contractions including thromboxane A₂ . Here, we examined effects of PLA₂ inhibitors on contractions of human prostate tissues.

Methods: Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS) and by α₁ -adrenergic agonists in an organ bath, after application of the cytosolic PLA₂ inhibitors ASB14780 and AACOCF3, the secretory PLA₂ inhibitor YM26734, the leukotriene receptor antagonist montelukast, or of solvent to controls.

Results: Frequency-dependent contractions of human prostate tissues induced by EFS were inhibited by 25% at 8 Hz, 38% at 16 Hz and 37% at 32 Hz by ASB14780 (1 µM), and by 32% at 16 Hz and 22% at 32 Hz by AACOCF3 (10 µM). None of both inhibitors affected contractions induced by noradrenaline, phenylephrine or methoxamine. YM26734 (3 µM) and montelukast (0.3 and 1 µM) neither affected EFS-induced contractions, nor contractions by α₁ -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM).

Conclusions: Our findings suggest presynaptic PLA₂ functions in prostate smooth muscle contraction, while contractions induced by α₁ -adrenergic agonists occur PLA₂ -independent. Lacking sensitivity to montelukast excludes an involvement of PLA₂ -derived leukotrienes in promotion of contractile neurotransmission.

Keywords: benign prostatic hyperplasia (BPH); lower urinary tract symptoms (LUTS); phospholipase; prostate smooth muscle contraction; voiding symptoms; α1-adrenoceptor; α1-blocker.