Taurine activates strychnine-sensitive glycine receptors in neurons freshly isolated from nucleus accumbens of young rats.
Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs, is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12- to 21-day old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (IGly and ITau) with an EC50 of 0.12 and 1.25 mM, respectively. The reversal potential of IGly or ITau was 0 mV in conventional whole cell mode and -30 mV in gramicidin-perforated mode. At concentrations <1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC50 of 60 nM and 36.5 microM for IGly, and 40 nM and 42.2 microM for ITau) but were insensitive to 10 microM bicuculline. The currents elicited by taurine (< or =1 mM) showed complete cross-desensitization with IGly, but none with gamma-aminobutyric acid (GABA)-induced currents (IGABA). However, ITau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with IGABA, and it was substantially antagonized by 10 microM bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABAA receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.
Jiang
Zhenglin
Z
Departments of Anesthesiology, Pharmacology, and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103-2714, USA.
Krnjević
Kresimir
K
Wang
Fushun
F
Ye
Jiang Hong
JH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects* / Q000502:physiology; D013654:Taurine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001640:Bicuculline; D018756:GABA Antagonists; D005998:Glycine; D010852:Picrotoxin; D018009:Receptors, Glycine; D013654:Taurine; D005680:gamma-Aminobutyric Acid; C027822:strychnine receptor