Abstract
To examine purinergic signaling in human vas deferens. To study contractile responses of the scrotal vas deferens. Research department of a university teaching hospital. Undergoing vasectomy or orchidectomy (aged 27-88 years, n = 14). Vasectomy or orchidectomy. 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 alpha1 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. 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 microM). Contractions to ATP and alpha,beta-meATP (EC50 = 6.27 microM) suggested that the functional receptor was P2X1 and/or P2X3. However, immunohistochemistry demonstrated P2X1, but not P2X3, receptor immunoreactivity on the smooth muscle cells. 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.
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