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.
Department of Physiology, Medical School, University of Birmingham, U.K.
A P
AP
Yusof
J H
JH
Coote
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D009433:Neural Inhibition; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013346:Subarachnoid Space; D013564:Sympathetic Nervous System / Q000502:physiology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin