Excitatory and inhibitory actions of intrathecally administered 5-hydroxytryptamine on sympathetic nerve activity in the rat.

In chloralose/urethane anaesthetised rats the effect of intrathecal (i.t.) administration of 5-hydroxytryptamine (5-HT) on activity in sympathetic nerves to the kidney was studied. Intrathecal 5-HT (20-100 micrograms, 10 microliter) increased activity in renal nerves (mean change for 50 micrograms dose 157% +/- 39). At higher doses of 5-HT the initial excitatory response was followed by inhibition 64% +/- 15. Intrathecally, alpha methyl 5-HT (10-400 micrograms) mimicked only the inhibitory action of 5-HT in a dose-dependent manner. These inhibitions were completely antagonised by i.t. ketanserin (25-100 micrograms). Intrathecal 2 methyl 5-HT (10-200 micrograms) had little effect on renal nerve activity. Intrathecal 5 carboxyamidotryptamine (10-200 micrograms) had a more powerful excitatory action on renal nerve activity than did 5-HT. Intrathecally, 8 OH-DPAT (10-200 micrograms) was without effect. Neither the inhibitory action of 5-HT or the excitatory action was affected by i.t. ICS 205 930 (1-10 micrograms) or MDL 72222 (200 micrograms). It was concluded that the actions of 5-HT were within the spinal cord and that the inhibitory effect on sympathetic activity is mediated via a 5-HT2-like receptor whilst the receptors involved in the excitatory action of 5-HT are not M- or 5-HT3-like but appear to be more like the 5-HT1 subtype.