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

Immunohistochemical studies demonstrated abundant P2X(1)-receptor immunoreactivity colocalized with alpha-actin within the fibromuscular stroma of the guinea pig prostate. P2X(2)-, P2X(3)- and P2X(4)-receptor immunoreactivity was absent. alphabetamethylene 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 microM). Responses to 1-2 Hz were unaffected. ARL 67156 (6-N, N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5-triphosphate; 100 microM) 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 microM)-sensitive contractions. The rank order of potency was: alphabetamethylene ATP>2methylthio ATP=betagammamethylene 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.