The purinergic component of human vas deferens contraction

Objective: To examine purinergic signaling in human vas deferens. Design: To study contractile responses of the scrotal vas deferens. Setting: Research department of a university teaching hospital. Patient(s): Undergoing vasectomy or orchidectomy (aged 27-88 years, n = 14). Intervention(s): Vasectomy or orchidectomy. Main Outcome Measure(s): Strips of vas deferens were suspended in an organ bath and subjected to electrical stimulation to establish frequency-response curves. These stimulations were repeated in the presence of pyridoxalphosphate-6-azophenyl-2',4'-disulfoinc acid (PPADS, P2 receptor antagonist), prazosin (adrenergic alpha(1) antagonist), and tetrodotoxin. Concentration-response curves were constructed to noradrenaline and the P2X agonists ATP and alpha,beta-methylene ATP (alpha,beta-meATP). The P2X receptor subtype distribution was assessed by immunohistochemistry using specific antibodies. Result(s): The response at 32 Hz in the presence of PPADS was reduced by 40% and in the presence of prazosin by 80%. Noradrenaline caused concentration-dependent contractions (EC50 = 11.8 mu M). Contractions to ATP and alpha,beta-meATP (EC50 = 6.27 mu M) suggested that the functional receptor was P2X(1) and/or P2X(3). However. immunohistochemistry demonstrated P2X(1), but not P2X(3), receptor immunoreactivity on the smooth muscle cells. Conclusion(s): This study demonstrated that ATP is a co-transmitter with noradrenaline in the contraction of the human vas deferens predominantly acting through the P2X(1) receptor.