Effects of agmatine on the electrical activity of subfornical organ neurons.
The aim of this study was to investigate the effects of agmatine (Agm) on the electrical activity of neurons in subfornical organ (SFO) slices using extracellular recording technique. The results are as follows. (1) In response to the application of Agm (1.0 micromol/L) into the superfusate for 2 min, the discharge rate of 24/28 (85.7%) subfornical neurons was decreased significantly, while the discharge rate of 4/28 (14.3%) neurons were not affected. (2) Pretreatment with L-glutamate (0.3 mmol/L) led to a marked increase in the discharge rate of 19/24 (79.2%) subfornical neurons in an epileptiform pattern and the activity of the remaining 5/24 (20.8%) neurons was unaffected. By application of Agm (1.0 micromol/L) into the superfusate for 2 min, the epileptiform dicharge of 15/19 (78.9%) neurons was suppressed significantly, while that of the other 4 (21.1%) neurons was not inhibited. (3) In 12 neurons, perfusion of the selective L-type calcium channel agonist, Bay K-8644 (0.1 micromol/L), induced a significant increase in the discharge rate of 10/12 (83.3%) neurons, while the other 2 (16.7%) neurons showed no change. The increased discharge of 8/10 (80%) neurons was reduced by application of Agm (1.0 micromol/L) into the superfusate and that of 2/10 (20%) neurons was not affected. (4) Application of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 micromol/L) into the superfusate also significantly increased the discharge rate of 6/9 (66.7%) neurons, and that of 3/9 (33.3%) neurons had no response. Agm (1.0 micromol/L) applied into the superfusate reduced the increased discharge of all 6/6 (100%) neurons. These results suggest that Agm can inhibit the spontaneous discharge, and L-glutamate, Bay K-8644- or L-NAME-induced discharge of neurons in SFO. These inhibitory effects of Agm may be related to the blockade of NMDA receptors and reduction in calcium influx in SFO neurons.
Wang
Ze-Min
ZM
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Ji
Shu-Mei
SM
Zhang
Hao
H
Sun
Guang-Qi
GQ
Wang
Zhi-An
ZA
He
Rui-Rong
RR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013356:Subfornical Organ / Q000187:drug effects / Q000502:physiology*
D002120:Calcium Channel Agonists; D011955:Receptors, Drug; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000376:Agmatine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester