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

BACKGROUND

Phospholipases A (PLA ) may be involved in α -adrenergic contraction by formation of thromboxane A in different smooth muscle types. However, whether this mechanism occurs with α -adrenergic contractions of the prostate, is still unknown. While α -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 A . Here, we examined effects of PLA 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 α -adrenergic agonists in an organ bath, after application of the cytosolic PLA inhibitors ASB14780 and AACOCF3, the secretory PLA 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 α -adrenergic agonists, while all contractions were substantially inhibited by silodosin (100 nM).

CONCLUSIONS

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