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Specific binding of pipecolic acid to bovine synaptic

Journal Article · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6992602
Pipecolic acid (PA) is an intermediate of L-lysine metabolism in the brain. PA has been shown to have an interaction with the gamma-aminobutyric acid (GABA) transmission. /sup 3/H-PA binding to crude synaptic membranes of bovine brain was studied in an attempt to identify and characterize the specific binding of PA to its own membrane binding site independent of the GABA receptor. Specific /sup 3/H-PA binding to synaptic membrane is saturable. Equilibrium between /sup 3/H-PA and the binding sites is reached within 60 min with a linear dependency on the membrane protein concentration up to 2 mg/ml. This binding is dependent on Na/sup +/ and Mg/sup 2 +/. Dialysis of the synaptic membrane increases the signal to noise ratio of /sup 3/H-PA binding. Scatchard analysis revealed that dialysis for 3 days significantly increased the maximal binding capacity over that for 20 day dialysis (B/sub max/ from 0.32 to 1.7 pmol/mg) without significantly altering the apparent dissociation constant (K/sub D/ = 55 to 67 nM). Displacement of specific /sup 3/H-PA binding by L- and D-PA is stereospecific (IC/sub 50/ = 4.6 x 10/sup -6/M and 5.6 x 10/sup -5/M). IC/sub 50/ for GABA and L-proline are 3.6 x 10/sup -4/M and 6.4 x 10/sup -6/M. Nipecotic acid, isonipecotic acid, bicuculine, hexobarbital, picrotoxin and piperidine are not active. /sup 3/H-PA binding is inhibited by GTP in a concentration (10/sup -6/ - 10/sup -4/ M) dependent manner, suggesting that PA binding to brain membrane may be coupled to adenylate cyclase in the brain.
Research Organization:
Univ. of Maryland Dental School, Baltimore, MD
OSTI ID:
6992602
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English