S. Boehm, NORADRENALINE RELEASE FROM RAT SYMPATHETIC NEURONS EVOKED BY P-2-PURINOCEPTOR ACTIVATION, Naunyn-Schmiedeberg's archives of pharmacology, 350(5), 1994, pp. 454-458
The effects of ATP and analogues on the release of previously incorpor
ated H-3-noradrenaline were studied in cultured sympathetic neurons de
rived from superior cervical ganglia of neonatal rats. Electrical fiel
d stimulation (40 mA at 3 Hz) of the neurons for 10 s markedly enhance
d the outflow of tritium. ATP applied for 5 s to 2 min at concentratio
ns of 0.01 to 1 mmol/l caused a time- and concentration-dependent over
flow with half maximal effects at about 10 s and 100 mu mol/l, respect
ively. 2-Methylthio-ATP was equipotent to ATP in inducing H-3-overflow
ADP (100 mu mol/l), when applied for 2 min, also caused a small H-3-o
verflow, but alpha, beta- methylene-ATP (100 mu mol/l), AMP (100 mu mo
l/l), R(-)N-6-(2-phenylsiopropyl)-adenosine (R(-)-PIA; 10 mu mol/l) an
d 5'-N-ethylcarboxamidoadenosine (NECA; 1 mu mol/l) did not. The H-3-o
verflow induced by 10 s applications of 100 mu mol/l ATP was abolished
by suramin (100 mu mol/l) and reduced by about 70% by reactive blue 2
(3 mu mol/l). Electrically evoked overflow in contrast, was slightly
enhanced by suramin, but not modified by reactive blue 2. Xanthine ami
ne congener (10 mu mol/l) and hexamethonium (10 mu mol/l) did not alte
r ATP-evoked release. Removal of extracellular Ca2+ from the medium re
duced ATP- and electrically induced overflow by about 95%. Tetrodotoxi
n (1 mu mol/l) abolished electrically evoked H-3-overflow but inhibite
d ATP-induced overflow by only 70%. The alpha(2)-adrenoceptor agonist
UK 14,304 at a concentration of 1 mu mol/l diminished both electricall
y and ATP-evoked tritium overflow by approximately 70%. These results
indicate that activation of P-2-purinoceptors stimulates noradrenaline
release from rat sympathetic neurons. The release resembles electrica
lly induced transmitter release, but additional mechanisms may contrib
ute.