The actions of a charged melatonin receptor ligand, TMEPI, and an irreversible MT2 receptor agonist, BMNEP, on mouse hippocampal evoked potentials in vitro.
We have previously determined that melatonin modulates hippocampal synaptic transmission in a biphasic way: an initial depression was followed by a recovery/amplification phase. Here we describe the influence of two novel melatonin receptor ligands, BMNEP (N-bromoacetyl-2-iodo-5-methoxytryptamine) and TMPEI (N-[2-(2-Trimethylammoniumethyleneoxy-7-methoxy)ethyl]propionamide iodide), on the population spike (PS) and excitatory postsynaptic potentials (EPSP) recorded from mouse hippocampal slices. BMNEP, which specifically alkylates and constitutively activates the MT2 melatonin receptor, mimicked the first phase of melatonin's action by irreversibly depressing both the PS and EPSP. TMPEI, a charged ligand of plasma membrane melatonin receptors, amplified those potentials in a manner similar to the effect of melatonin observed during the second, recovery phase. Melatonin had no influence on the potentials amplified by the action of TMPEI. Our results suggest that the biphasic, receptor-dependent action of melatonin and its analogs modulates the efficiency of the hippocampal glutamergic synapse and is most likely mediated through two different, sequentially occurring mechanisms.
Department of Biology and CSI/IBR Center for Developmental Neuroscience, The College of Staten Island/CUNY, 2800 Victory Boulevard, Staten Island, NY 10314, USA.
Yasir
Y
El-Sherif
Paula
P
Witt-Enderby
Pui-Kai
PK
Li
Jene
J
Tesoriero
Michael V
MV
Hogan
Andrzej
A
Wieraszko
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000577:Amides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008024:Ligands; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008668:Metallothionein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000494:pharmacology*; D044094:Receptors, Melatonin / Q000378:metabolism*; D013997:Time Factors
D000577:Amides; D008024:Ligands; C491054:Mt2 protein, mouse; D000644:Quaternary Ammonium Compounds; D044094:Receptors, Melatonin; C070373:N-bromoacetyl-2-iodo-5-methoxytryptamine; D008735:5-Methoxytryptamine; D008668:Metallothionein; D008550:Melatonin