N-Acetylaspartylglutamate: possible role as the neurotransmitter of the lateral olfactory tract.

Abstract

N-Acetylaspartylglutamate, an endogenous brain peptide that binds with high affinity to a subpopulation of glutamate-binding sites in rat brain, is excitatory on rat piriform cortex pyramidal cells studied in a perfused brain slice. Both the monosynaptic excitation of the pyramidal cells elicited by stimulation of the lateral olfactory tract and the response to N-acetylaspartylglutamate were blocked by DL-2-amino-4-phosphonobutyrate but not by other excitatory amino acid antagonists. Responses to glutamate and aspartate, previously considered to be candidates as the lateral olfactory tract transmitter, were unaffected by 2-amino-4-phosphonobutyrate. Three days after unilateral bulbectomy there was a significant decrease in concentrations of N-acetylaspartylglutamate as well as aspartate, N-acetylaspartate, and y-aminobutyrate in the pyriform cortex of the side from which the olfactory bulb had been removed. These results are consistent with the possibility that N-acetylaspartylglutamate is the endogenous transmitter of the lateral olfactory tract.

Possible presynaptic actions of 2‐amino‐4‐phosphonobutyrate in rat olfactory cortex

“…Certainly, inhibition of transmitter release by lowering extracellular calcium levels (Figure 4a) or reducing stimulus intensity (Figures 2 and 3b) mimic the effects of APB on synaptic facilitation. Second, although there is controversy regarding the identity of the LOT transmitter(s) (ffrench-Mullen et al, 1985;Collins, 1986), APB Amplitude of conditioning response (mV) Figure 6 Drug effects on the increase in synaptic facilitation produced by 2-amino-4-phosphonobutyrate (APB) (1 mM). Each point is the mean % facilitation (n between 3 and 6) measured at fixed amplitudes of the conditioning response in slices stimulated at a constant conditioning interval of 100 ms. For clarity, the s. (Surtees & Collins, 1985;Collins & Brown, 1986).…”

An explanation for the purported excitation of piriform cortical neurons by N-acetyl-L-aspartyl-L-glutamic acid (NAAG).

“…Tangential (1,11,12,14) (400-600 Aum thick) and parasagittal (13) (450 and 600 .&m thick) slices of rat piriform cortex were obtained from male Sprague-Dawley (Bio-Lab, Saint Paul, MN) rats (26-60 days old). The slices were incubated in oxygenated medium (22-280C) for at least 1 hr.…”

“…Two media were used (12,17), differing-primarily in potassium ion concentration (5 mM versus 3.3 mM); no differences in evoked responses were noted. Bipolar stimulation was delivered to the fibers of the LOT (1,(11)(12)(13)(14) via a pair of Teflon-coated stainless-steel wires (0.003 inch; 1 inch = 2.54 cm) at 0.1 Hz, using either single (0.1 msec) or paired (2 x 0.05 msec, separated by 60 msec) stimuli (0-40 V). Field potential and single-unit responses were recorded using glass micropipettes filled with 2 M NaCl (3-15 MfI impedance), placed in the cell body layer, as described below.…”

“…Of the electrophysiological evidence, the strongest support for the role of NAAG as an excitant comes from the rat piriform cortex (1,(11)(12)(13)(14), where iontophoresis of NAAG purified from rat brain was reported to evoke single neuron spiking that was inhibited by DL-2-amino-4-phosphonobutanoic acid (DL-AP4) (1). Since DL-AP4 also inhibited unit responses evoked by stimulation ofthe lateral olfactory tract (LOT), the authors suggested that NAAG may be the endogenous transmitter of the LOT.…”

“…Data from electrophysiological (1)(2)(3)(4)(5), localization (6,7), release (8,9), and degradation (10) studies suggest that the endogenous dipeptide N-acetyl-L-aspartyl-L-glutamic acid (NAAG) may serve as an excitatory neurotransmitter in certain areas of the mammalian central nervous system. Of the electrophysiological evidence, the strongest support for the role of NAAG as an excitant comes from the rat piriform cortex (1,(11)(12)(13)(14), where iontophoresis of NAAG purified from rat brain was reported to evoke single neuron spiking that was inhibited by DL-2-amino-4-phosphonobutanoic acid (DL-AP4) (1).…”