Glycine-related amino acids stereoselectively affect N-methyl-D-aspartate receptor-mediated contractions of guinea pig ileum: comparison with the inhibition of strychnine-insensitive [3H]glycine binding to rat cortical membranes.
Ten microM glycine, D-serine and D-alanine potentiated L-glutamate (30 microM)-induced contractions of the guinea pig ileum by an average of 35, 53 and 24%, respectively. On the contrary, D-cysteine, at the same concentration, caused a 21% inhibition of the contractile response to L-glutamate. This inhibitory effect of D-cysteine was abolished by 10 microM glycine. The corresponding L-isomers of these amino acids, namely L-serine, L-alanine and L-cysteine and the other amino acids tested, possessed negligible activity or were inactive in this test. The IC50 values of the same compounds for strychnine-insensitive binding of [3H]glycine (20 nM) to cortical membranes from the brain of the rat were: 0.26 microM, glycine; 1.2 microM, D-serine; 2.1 microM, D-alanine; 8.6 microM, D-cysteine; 51 microM, L-serine; 90 microM, L-alanine; greater than 1000 microM, L-cysteine. On the whole, these results point out a strict requirement for stereoselectivity for both of the effects examined. In addition, the results obtained in the ileum preparation suggest that D-cysteine may act as an antagonist, rather than as an agonist at the glycine site which regulates the responses of N-methyl-D-aspartate receptors.
Galli
A
A
Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.
Franchi-Micheli
S
S
Mori
F
F
Luzzi
S
S
Zilletti
L
L
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013237:Stereoisomerism; D013331:Strychnine / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007736:Kynurenic Acid; D013331:Strychnine; D005998:Glycine