AbstractBACKGROUNDThe prostate gland contains numerous neuroendocrine cells (PNECs) innervated by adrenergic neurons. PNECs are believed to influence the growth and physiological function of the prostate gland via paracrine release of hormones.MATERIALS AND METHODSUsing fura‐2 fluorescence measurement and patch‐clamp techniques, we investigated the effects of adrenergic stimulation on cytosolic concentration of Ca2+ ([Ca2+]c) and high voltage‐activated Ca2+ channel currents (HVA‐ICa) of the putative rat prostate neuroendocrine cells (RPNECs) freshly isolated by an enzymic digestion.RESULTSNoradrenaline (NA, 1 μM) induced a sharp, transient increase of [Ca2+]c measured by the fura‐2 fluorescence. Pharmacological studies showed that α1‐adrenoceptors (α1‐ARs) coupled with PLC/IP3 signaling pathway induce the release of stored Ca2+, which subsequently recruits store‐operated Ca2+ entry pathways. In the whole‐cell voltage clamp experiment, NA decreased the amplitude of HVA‐ICa by 40%, which was mimicked by an α2‐AR agonist (UK14304) but not by an α1‐AR agonist (phenyleprine). After selective blockade of N‐type Ca2+ channels by ω‐conotoxin GVIA, the addition of NA showed no further inhibition on the remaining L‐type Ca2+ channel currents. The adrenergic inhibition of HVA‐ICa was partially prevented by the pretreatment with pertussis toxin (PTX) (5 μg/ml, 4 hr, 37°C).CONCLUSIONSRPNECs express both α1‐ and α2‐ARs, signaling the release of stored Ca2+ and the inhibition of N‐type Ca2+ channels, respectively. Prostate 57: 99–110, 2003. © 2003 Wiley‐Liss, Inc.