(-)Epigallocatechin-3-gallate inhibits the spontaneous firing of rat locus coeruleus neuron.
(-)Epigallocatechin-3-gallate (EGCG), a tea catechin, has been known to cause many biological actions, such as anxiolytic and hypotensive effects in behavioral studies. However, to date, few reports investigate its neuronal modulation. In this study, intracellular recording was used to test the neuronal modulation of different catechins on locus coeruleus (LC) neuron, which has been demonstrated to be affected by cardiovascular function regulation and stressful events. Several catechins (1 -- 1,000 microM) were tested, including: (-)catechin (C), (-)catechingallate (CG), (-)epicatechin (EC), (-)epicatechin-3-gallate (ECG), (?)epigallocatechin (EGC) and EGCG. The results showed that catechins EC, ECG, EGC and EGCG could inhibit the spontaneous firing of the LC neurons; furthermore, these catechins show potency and efficacy in the order of EGCG>ECG>EC approximately EGC. Among the tested catechins, EGCG was the most potent in inhibiting LC's spontaneous firing with IC(50) of 20.5 microM. This caused us to further examine the EGCG's desensitization and tolerance properties. When continuously administering EGCG at 1 -- 300 microM for 20 min, no acute desensitization appeared. However, repeated applications of 300 microM EGCG at 5 min each time showed different results. The second and third applications induced less responses compared to that of the first application, suggesting a development of tolerance towards EGCG in inhibiting LC neuronal activity. Our data suggest that EGCG can inhibit LC neuron's spontaneous firing in a dose-dependent manner, with developed tolerance only when high concentration of EGCG is repeatedly applied.
Chang
Kuo-Chi
KC
Department of Nursing, St. Mary's Medicine, Nursing and Management College, Yilan County 26604, Taiwan, ROC.
Yang
Jia Jang
JJ
Wang-Hsu
Elizabeth Che-Hsiang
EC
Chiu
Tsai-Hsien
TH
Hsu
Fu-Chun
FC
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; C417939:catechin gallate; D002392:Catechin; C045651:epigallocatechin gallate; C057580:gallocatechol; D009638:Norepinephrine