Endogenous noradrenaline impairs the prostaglandin-induced inhibition of noradrenaline release.

The effects of prostaglandin E2 (PGE2) on electrically evoked noradrenaline release in rat brain cortex were studied under conditions under which autoinhibition of release was avoided. When stimulation was carried out with 36 pulses at 3 Hz, 1 mumol/l PGE2, produced about 50% inhibition of release. In the presence of the alpha 2-adrenoceptor antagonist yohimbine (1 mumol/l) the effect of PGE2 was markedly increased. When release was elicited by 3 pulses/100 Hz the period of stimulation was too short to permit development of autoinhibition by released noradrenaline. Then the concentration-response-curve for PGE2 was very similar to that obtained under the above conditions (36 pulses/3 Hz, in the presence of yohimbine). These data suggest that both the alpha 2-adrenoceptor and the PGE2-receptor are linked to a common pathway. Since indometacin (10 mumol/l) did not enhance evoked transmitter release, an influence of endogenous PG's on in vitro release of noradrenaline from rat brain cortex slices can be excluded.