MODULATION OF NEURAL NORADRENALINE AND ATP RELEASE BY ANGIOTENSIN-II AND PROSTAGLANDIN E(2) IN GUINEA-PIG VAS-DEFERENS

Effects of angiotensin II and prostaglandin E(2) on contractions, release of noradrenaline and release of ATP elicited by electrical stimulation (210 pulses, 7 Hz) were studied in the isolated vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of tritium after preincubation with [H-3]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. In some experiments postsynaptic alpha(1)-adrenoceptors and P-2x-purinoceptors were blocked by prazosin and suramin, respectively, to isolate the neural fraction of the overflow of ATP. Electrical stimulation elicited an overflow of tritium and ATP and, in the absence of prazosin and suramin, contraction. In the absence of prazosin and suramin, angiotensin II(1-100 nM) enhanced contractions as well as the evoked overflow of tritium and ATP. All parameters were increased by about the same percentage for a given concentration of angiotensin II. The effect of prostaglandin E(2) (1-100 nM) was complex. Contractions were mainly enhanced, the evoked overflow of tritium was reduced, whereas the evoked overflow of ATP was predominantly increased. No or almost no contraction remained in the presence of prazosin and suramin, and the evoked overflow of ATP was decreased to about 16%. Angiotensin II (1-100 nM) again enhanced the evoked overflow of tritium and ATP. Both were increased by about the same percentage for a given concentration of angiotensin II and also were increased by about the same percentage as obtained in the absence of prazosin and suramin. Prostaglandin E(2) (1-100 nM) decreased the evoked overflow of tritium and ATP in the presence of prazosin and suramin, both by about the same percentage at a given prostaglandin E(2) concentration. It is concluded that neural release of ATP, like the release of noradrenaline, is presynaptically facilitated by angiotensin II and depressed by prostaglandin E(2) In the case of angiotensin II, increases in neural and postsynaptic ATP release contribute to the increase in ATP overflow observed in the absence of prazosin and suramin. In the case of prostaglandin E(2), an increase in postsynaptic ATP release can override the reduction in neural ATP release and give rise to an increase in ATP overflow in the absence of prazosin and suramin. No evidence for a differential modulation of neural noradrenaline versus ATP release was found.