Effects of ethylenediamine--a putative GABA-releasing agent--on rat hippocampal slices and neocortical activity in vivo.
The simple diamine diaminoethane (ethylenediamine, EDA) has been shown to activate GABA receptors in the central and peripheral nervous systems, partly by a direct action and partly by releasing endogenous GABA. These effects have been shown to be produced by the complexation of EDA with bicarbonate to form a carbamate. The present work has compared EDA, GABA and β-alanine responses in rat CA1 neurons using extracellular and intracellular recordings, as well as neocortical evoked potentials in vivo. Superfusion of GABA onto hippocampal slices produced depolarisation and a decrease of field epsps, both effects fading rapidly, but showing sensitivity to blockade by bicuculline. EDA produced an initial hyperpolarisation and increase of extracellular field epsp size with no fade and only partial sensitivity to bicuculline, with subsequent depolarisation, while β-alanine produces a much larger underlying hyperpolarisation and increase in fepsps, followed by depolarisation and inhibition of fepsps. The responses to β-alanine, but not GABA or EDA, were blocked by strychnine. In vivo experiments, recording somatosensory evoked potentials, confirmed that EDA produced an initial increase followed by depression, and that this effect was not fully blocked by bicuculline. Overall the results indicate that EDA has actions in addition to the activation of GABA receptors. These actions are not attributable to activation of β-alanine-sensitive glycine receptors, but may involve the activation of sites sensitive to adipic acid, which is structurally equivalent to the dicarbamate of EDA. The results emphasise the complex pharmacology of simple amines in bicarbonate-containing solutions.
Neuroscience and Molecular Pharmacology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. Trevor.Stone@glasgow.ac.uk
Trevor W
TW
Stone
Caleb
C
Lui
Jonas I
JI
Addae
D000272:Adipates / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018682:GABA Agents / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D000272:Adipates; D001639:Bicarbonates; D005029:Ethylenediamines; D018682:GABA Agents; D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid; C031234:ethylenediamine; C029900:adipic acid; D001640:Bicuculline