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, rele ase of noradrenaline and release of ATP elicited by electrical stimula tion (210 pulses, 7 Hz) were studied in the isolated vas deferens of t he guinea pig. Release of noradrenaline was assessed as overflow of tr itium after preincubation with [H-3]-noradrenaline. ATP was measured b y means of the luciferin-luciferase technique. In some experiments pos tsynaptic alpha(1)-adrenoceptors and P-2x-purinoceptors were blocked b y prazosin and suramin, respectively, to isolate the neural fraction o f the overflow of ATP. Electrical stimulation elicited an overflow of tritium and ATP and, in the absence of prazosin and suramin, contracti on. In the absence of prazosin and suramin, angiotensin II(1-100 nM) e nhanced contractions as well as the evoked overflow of tritium and ATP . All parameters were increased by about the same percentage for a giv en concentration of angiotensin II. The effect of prostaglandin E(2) ( 1-100 nM) was complex. Contractions were mainly enhanced, the evoked o verflow 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 d ecreased to about 16%. Angiotensin II (1-100 nM) again enhanced the ev oked overflow of tritium and ATP. Both were increased by about the sam e 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 evok ed overflow of tritium and ATP in the presence of prazosin and suramin , both by about the same percentage at a given prostaglandin E(2) conc entration. It is concluded that neural release of ATP, like the releas e of noradrenaline, is presynaptically facilitated by angiotensin II a nd depressed by prostaglandin E(2) In the case of angiotensin II, incr eases in neural and postsynaptic ATP release contribute to the increas e in ATP overflow observed in the absence of prazosin and suramin. In the case of prostaglandin E(2), an increase in postsynaptic ATP releas e 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 e vidence for a differential modulation of neural noradrenaline versus A TP release was found.