The effect of 1-phenylephrine (1-PE), an alpha (1)-receptor agonist, was in
vestigated on the release of tritiated norepinephrine ([H-3]NE). Pairs of g
uinea pig vasa deferentia were loaded with [H-3]NE, superfused continuously
, and stimulated electrically. 1-PE (10, 100 muM) enhanced the basal releas
e of tritium in concentration-dependent manner. The stimulation-evoked rele
ase of radioactivity was significantly increased by 100 muM 1-PE. Both basa
l and stimulation-evoked release by 1-PE were reduced by desipramine (10 CI
M), a monoamine uptake inhibitor. The effect of 1-PE on basal release was i
ndependent on extracellular Ca2+ concentration ([Ca2+](o)) and alpha (1)-ad
renoceptor blockade. However, the 1-PE-induced release was temperature depe
ndent: at low temperature 1-PE failed to increase either basal or stimulati
on-evoked release of NE. Using three different temperatures (7, 12, 17 degr
eesC, respectively), it was found that basal release was blocked at all thr
ee temperature values but the stimulation-evoked release was inhibited only
at the lower values. The effect of 1-PE on the NE release appears to invol
ve a desipramine-, and temperature-sensitive process. These results suggest
that a non-receptorial and direct carrier-mediated mechanism is involved i
n NE releasing effect of 1-PE. (C) 2001 Elsevier Science Ltd. All rights re
served.