Effect of beta-N-oxalylamino-L-alanine on cerebellar cGMP level in vivo.
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.
Department of Neurology, University of Palermo, Italy.
V
V
La Bella
F
F
Brighina
F
F
Piccoli
R
R
Guarneri
D000284:Administration, Oral; D000599:Amino Acids, Diamino; D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000599:Amino Acids, Diamino; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D006152:Cyclic GMP