DIFFERENCES BETWEEN THE REGULATION OF NORADRENALINE AND ATP RELEASE

1 We have studied the effects of adrenergic receptor agonists and anta gonists and various calcium channel antagonists on the overflow of ade nine nucleotides (ATP, ADP, AMP), adenosine (ADO) and noradrenaline (N A) from superfused guinea-pig vasa deferentia evoked by electrical fie ld stimulation (EFS). 2 Samples of superfusate were taken at 10 s inte rvals for analysis of purines (HPLC with fluorescence detection) and o f NA (HPLC with electrochemical detection). During 1 min of EFS the ov erflow of ATP peaked at about 20 s and then abruptly decreased even th ough stimulation continued. The overflow of NA reached a peak at about 40 s and remained at a constant level for the duration of the stimula tion. 3 Pretreatment with the alpha(2)-receptor antagonists idazoxan a nd yohimbine produced a substantial increase in the overflow of NA and a lesser increase in the overflow of ATP, indicating that endogenousl y released NA has a greater influence on its own release than on that of ATP. Interestingly, certain alpha(2)-agonists, e.g. xylazine and cl onidine, 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 c alcium channel antagonist omega-conotoxin reduced the EFS-evoked relea se of NA to a greater extent than ATP while the P-type calcium channel antagonist omega-agatoxin did the reverse. These results indicate tha t NA release may be more dependent on calcium influx through N-type ch annels 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-transmitte rs originate from different release sites in adrenergic nerves.