Adenosine 5′-triphosphate and noradrenaline are excitatory cotransmitters to the fibromuscular stroma of the guinea pig prostate gland

Abstract

Immunohistochemical studies demonstrated abundant P2X 1-receptor immunoreactivity colocalized with α-actin within the fibromuscular stroma of the guinea pig prostate. P2X 2-, P2X 3- and P2X 4-receptor immunoreactivity was absent. αβmethylene Adenosine 5′-triphosphate (ATP) attenuated contractile responses to electrical field stimulation (50 V, 0.5 ms, 5–20 Hz) in the absence and presence of prazosin (0.3 μM). Responses to 1–2 Hz were unaffected. ARL 67156 (6- N, N-Diethyl-β-γ-dibromomethylene- d-adenosine-5-triphosphate; 100 μM) enhanced contractile responses to electrical field stimulation (50 V, 0.5 ms, 10–20 Hz). Concentration–response curves to exogenously applied ATP analogues on unstimulated preparations elicited concentration-dependent suramin (100 μM)-sensitive contractions. The rank order of potency was: αβmethylene ATP>2methylthio ATP=βγmethylene ATP>adenosine 5′-diphosphate (ADP)=ATP. Adenosine and adenosine 5′-monophosphate (AMP) did not produce contractile responses. These results demonstrate the presence of functional P2X 1-receptors within the fibromuscular stroma of the guinea pig prostate and suggest a cotransmitter role for ATP with noradrenaline during high-frequency stimulation.