Interaction of taurine and related compounds with GABAergic neurones in the nucleus raphe dorsalis.
The effects of GABAA (muscimol) and GABAB (baclofen) receptor agonists on spontaneous motor activity and food consumption of rats were compared to those produced by taurine and related compounds (3-aminopropanesulphonic acid, 5-aminovaleric acid, and guanidinoethanesulphonic acid). Local application of muscimol into the nucleus raphe dorsalis caused a dose-dependent increase in spontaneous motor activity. Muscimol-stimulated motor activity was blocked by picrotoxin. High doses relative to muscimol of 3-aminopropanesulphonic acid, guanidinoethanesulphonic acid, and 5-aminovaleric acid also attenuated the action of muscimol. Taurine by itself was ineffective on locomotion but enhanced the effect of a small dose of muscimol. Baclofen also stimulated activity but to a lesser extent than muscimol. Baclofen's stimulatory action on motor activity was partially blocked by 5-aminovaleric acid, whereas 3-aminopropanesulphonic acid was without effect. Muscimol and baclofen both increased food consumption of rats. Picrotoxin blocked this effect of muscimol, whereas the action of baclofen was blocked by 5-aminovaleric acid. Muscimol, taurine, and guanidinoethanesulphonic acid all reduced 5-hydroxytryptamine (5-HT) concentration in the hypothalamus. In radioligand binding studies, guanidinoethanesulphonic acid at micromolar concentrations displaced [3H]GABA from GABAA receptors. It is concluded that taurine may have a slight direct effect on GABA receptors but is more likely to act as an indirect neuromodulator of GABAergic neurotransmission in the brain.
Karolinska Institute, Department of Geriatric Medicine, Huddinge University Hospital, Sweden.
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Liljequist
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000502:physiology*
D011963:Receptors, GABA-A; D013654:Taurine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid