Differences between the regulation of noradrenaline and ATP release.

1. We have studied the effects of adrenergic receptor agonists and antagonists and various calcium channel antagonists on the overflow of adenine nucleotides (ATP, ADP, AMP), adenosine (ADO) and noradrenaline (NA) from superfused guinea-pig vasa deferentia evoked by electrical field stimulation (EFS). 2. Samples of superfusate were taken at 10 s intervals for analysis of purines (HPLC with fluorescence detection) and of NA (HPLC with electrochemical detection). During 1 min of EFS the overflow of ATP peaked at about 20 s and then abruptly decreased even though stimulation continued. The overflow of NA reached a peak at about 40 s and remained at a constant level for the duration of the stimulation. 3. Pretreatment with the alpha 2-receptor antagonists idazoxan and yohimbine produced a substantial increase in the overflow of NA and a lesser increase in the overflow of ATP, indicating that endogenously released NA has a greater influence on its own release than on that of ATP. Interestingly, certain alpha 2-agonists. e.g. xylazine and clonidine, produce a greater reduction in ATP release than NA. Together the results suggest that the release of ATP and NA may be regulated by different subsets of prejunctional alpha 2-receptors. 4. The N-type calcium channel antagonist omega-conotoxin reduced the EFS-evoked release of NA to a greater extent than ATP while the P-type calcium channel antagonist omega-agatoxin did the reverse. These results indicate that NA release may be more dependent on calcium influx through N-type channels whereas ATP release is coupled to calcium entry through P-type channels. 5. These differences in the pharmacological regulation of ATP and NA release lend credence to the idea that these two co-transmitters originate from different release sites in adrenergic nerves.