Norepinephrine and ATP are synergistic in the mouse vas deferens preparation

Norepinephrine (NE) and ATP are thought to be neurotransmitters involved with contractions of the mouse vas deferens (MVD) in vitro. The EC50 values of exogenously administered NE and ATP were 5.16 +/- 1.37 and 315.32 +/- 221.18 microM, respectively. Contractions of MVD induced by electrical field stimulation were blocked by alpha,beta-methylene adenosine-5'-triphosphate (purinergic desensitizer) and not by prazosin (alpha 1-adrenoceptor antagonist), suggesting that ATP is the predominant transmitter in this preparation. However, because the EC50 value for ATP was over 100-fold greater than that for NE, we performed isobolographic analysis comparing NE and ATP actions separately and together. Our results demonstrated a synergistic interaction of ATP and NE. At all ratios of ATP:NE examined, exogenous NE enhanced contractile responses to ATP. These data indicate that the co-transmitters, NE and ATP, in the MVD interact postjunctionally in a synergistic manner.