The purinergic component of human vas deferens contraction

ObjectiveTo examine purinergic signaling in human vas deferens.DesignTo study contractile responses of the scrotal vas deferens.SettingResearch 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′-disulfonic acid (PPADS, P2 receptor antagonist), prazosin (adrenergic α1 antagonist), and tetrodotoxin. Concentration–response curves were constructed to noradrenaline and the P2X agonists ATP and α,β-methylene ATP (α,β-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 μM). Contractions to ATP and α,β-meATP (EC50 = 6.27 μM) suggested that the functional receptor was P2X1 and/or P2X3. However, immunohistochemistry demonstrated P2X1, but not P2X3, 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 P2X1 receptor.