Activity of the conformationally rigid 2-amino-4-phosphonobutanoic acid (AP4) analogue (RS)-1-amino-3-(phosphonomethylene)cyclobutane-1-carboxylic acid (cyclobutylene AP5) on evoked responses in the perforant pathway of rat hippocampus.
The highly rigid and conformationally extended 2-amino-4-phosphonobutanoic acid (AP4) analogue (RS)-1-amino-3-(phosphonomethylene)-cyclobutane-1-carboxylic acid (cyclobutylene AP5) was synthesized and found to inhibit evoked responses in the rat lateral perforant path (LPP) with an IC50 of 41 (+/- 1.5 S.E.M.) microM and the medial perforant pathway with an IC50 of 218 (+/- 3.7 S.E.M.) microM. Furthermore, paired pulse potentiation experiments suggest that cyclobutylene AP5 acts, in part, at a presynaptic site in the LPP. Thus, cyclobutylene AP5 appears to act in a similar manner to L-AP4 in the perforant pathway. These data support the hypothesis that L-AP4 assumes an extended conformation at the L-AP4 receptor of the LPP.
Peterson
N L
NL
University of Minnesota, Department of Biochemistry, Minneapolis 55455.
Kroona
H B
HB
Johnson
R L
RL
Koerner
J F
JF
D000818:Animals; D003503:Cyclobutanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009434:Neural Pathways / Q000502:physiology; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D013758:Tetragastrin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D003503:Cyclobutanes; D009943:Organophosphorus Compounds; D013758:Tetragastrin; C066278:A 71623; C075263:1-amino-3-(phosphonomethylene)cyclobutane-1-carboxylic acid