The purinergic component of human vas deferens contraction.
OBJECTIVE
To examine purinergic signaling in human vas deferens.


METHODS
To study contractile responses of the scrotal vas deferens.


METHODS
Research department of a university teaching hospital.


METHODS
Undergoing vasectomy or orchidectomy (aged 27-88 years, n = 14).


METHODS
Vasectomy or orchidectomy.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Autonomic Neuroscience Centre, London, United Kingdom.
Frederick C L
FC
Banks
Gillian E
GE
Knight
Robert C
RC
Calvert
Cecil S
CS
Thompson
Robert J
RJ
Morgan
Geoffrey
G
Burnstock
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009919:Orchiectomy; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology*; D014659:Vasectomy
C546407:P2RX3 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate