C. Allgaier et al., EFFECTS OF 5-HT RECEPTOR AGONISTS ON DEPOLARIZATION-INDUCED [H-3] NORADRENALINE RELEASE IN RABBIT HIPPOCAMPUS AND HUMAN NEOCORTEX, British Journal of Pharmacology, 116(2), 1995, pp. 1769-1774
1 The present study attempted to determine whether noradrenaline (NA)
release in rabbit hippocampus and human neocortex is modulated by pres
ynaptic 5-hydroxytryptamine (5-HT) receptors. 2 Slices of rabbit hippo
campus and human neocortex, loaded with [H-3]-noradrenaline ([H-3]-NA)
were superfused and the effects of 5-hydroxytryptamine (5-HT) recepto
r ligands on electrically evoked [H-3]-NA release were investigated. 3
In rabbit hippocampus, 5-HT, 5-carboxamidotryptamine (5-CT; 32 mu M)
and 2-CH3-5-HT (32 mu M) increased [H-3]-NA release elicited with 360
pulses/3 Hz. Facilitation of transmitter release was not influenced by
the 5-HT3 receptor antagonist, tropisetron but was prevented by the a
lpha(2)-adrenoceptor antagonist, rauwolscine. When autoinhibition was
avoided by stimulating the tissue with 4 pulses/100 Hz (pseudo-one pul
se-(POP) stimulation), 2-CH3-5-HT decreased evoked transmitter release
, whereas 5-HT and 5-CT had no effect. Inhibition caused by 2-CH3-5-HT
was not affected by tropisetron but counteracted by the alpha(2)-adre
noceptor ligands, clonidine and rauwolscine. Inhibition caused by clon
idine was diminished in the presence of 5-CT or 2-CH3-5-HT. 4 In human
neocortex, [H-3]-NA release elicited with 360 pulses/3 Hz was increas
ed by 10 mu M 5-HT and 32 mu M 5-CT, whereas 2-CH3-5-HT was ineffectiv
e. [H-3]-NA release evoked with a modified POP stimulation (2 bursts o
f 4 pulses/100 Hz, 3.5 min apart) was not affected by 2-CH3-5-HT or 5-
CT. 5 The present results indicate that 5-HT, 2-CH3-5-HT and 5-CT can
act on presynaptic alpha(2)-autoreceptors as partial agonists (2-CH3-5
-HT; in rabbit hippocampal tissue) or antagonists (5-HT and 5-CT; in t
issue of rabbit hippocampus and human neocortex). Furthermore the exis
tence of autoinhibition dictates whether these drugs cause facilitatio
n of release, inhibition or have no effect.