Effect of beta-N-oxalylamino-l-alanine on cerebellar cGMP level in vivo

Abstract

Beta-N-oxalylamino-L-alanine (BOAA), a non-protein amino acid present in the seeds of Lathyrus Sativus (LS), is one of several neuroactive glutamate analogs reported to stimulate excitatory receptors and, in high concentrations, cause neuronal degeneration. In the present study, the in vivo acute effects of synthetic BOAA and LS seed extract were investigated on rat cerebellar cyclic GMP following intraperitoneal (10-100 mg/kg) or oral (100 mg/kg) administration of subconvulsive doses of toxin. Furthermore, the BOAA content in LS seeds and in the cerebellum of injected rats was determined by high performance liquid chromatograph analysis. A dose- and time-dependent increase of cerebellar cyclic guanosine monophosphate (cGMP) level was observed after intraperitoneal administration of synthetic BOAA or LS extract. The neurotoxin evoked a maximum stimulation 90 min after injection within the dose range of 50-75 mg/kg, elevating cGMP from basal levels of 5.3 +/- 0.5 pmol/mg protein to 15 +/- 1.3 pmol/mg protein. Similarly, the oral intake of LS-extracted neurotoxin resulted in the elevation of cGMP content. Kynurenic acid (300 mg/kg i.p.), a non specific excitatory amino acid antagonist, was effective in blocking LS BOAA-elicited cGMP enhancement. The data suggest that in the cerebellum acute administration of low concentrations of BOAA exert in vivo activation of glutamate receptors involved in the regulation of cGMP level.

Dietary Consumption ofLathyrus sativusSeeds Induces Behavioral Changes in the Rat

“…I. Poma (Institute of Agronomy, University of Palermo, Italy). The BOAA content in the LS seeds was estimated by HPLC analysis and ranged between 1 and 2 mg/g seeds (La Bella et al, 1993a). Conversely, in the CA seeds the content of neurotoxin, assayed by the same method, was negligible.…”

“…Recently, we have demonstrated that BOAA, either synthetic or extracted from LS seeds, when administered at subconvulsive doses to rats (50-100 mg/kg) is able to specifically increase cerebellar cyclic GMP levels (La Bella et al, 1993a) as well as to induce a down-regulation of non-NMDA glutamate receptors in the frontal cortex (La Bella et al, 1993b), thereby providing further support of a neurotoxin-mediated activation of glutamatergic synapse in vivo. However, neither neurological deficits nor behavioral abnormalities could be observed in the animals treated.…”

Comparative effect of dietary administration of Lathyrus sativus pulse on behaviour, neurotransmitter receptors and membrane permeability in rats and guinea pigs

“…17,18 Oral administration of nonconvulsant doses of β-L-ODAP to rats increases the cerebellar cyclic guanosine monophosphate (cGMP) level and induces downregulation of non-NMDA glutamate receptors in the frontal cortex. 19,20 However, little is known about the cellular mechanism of β-L-ODAP excitotoxicity on glutamate and other related neuroreceptors on systemic administration of lathyrus pulse. A recent study has demonstrated neurobehavioural changes in rats, in terms of increased open field activity following long-term dietary feeding of lathyrus pulse, 21 but further investigations are needed to elucidate the in vivo neurotoxicity of orally fed lathyrus pulse at different doses that can be achieved to the human population.…”