Biochemical research of phenyclidine reseptor : Interaction to specific bonding to the lower affinity receptor

Tutus Gusdinar; Robert Chicheportiche

doi:10.14499/indonesianjpharm0iss0pp190-198

Biochemical research of phenyclidine reseptor : Interaction to specific bonding to the lower affinity receptor

Tutus Gusdinar, Robert Chicheportiche

Abstract

Fixed concentration of MK-801 molecule had been used as a specific ligand for differenciating two kinds of phencyclidine (PCP) and thienylphencyclidine (TCP) receptors. By using several drug molecules which have different pharmacological action, as well as such molecular affinity (IC50) to the rat brain, it was obtained that both of these interacting receptors had equal character for its higher or lower affinity sites. The MK-801 molecule inhibited much strongly (IC50 is about 10 nM) fixation of 3HTCP to its higher affinity receptor and much weakly (IC50 is about 10 μM) fixation of 3H-PCP to its lower affinity receptor. The MK-801 molecule could be used as well for differenciating two 3H-TCP receptors, the higher and the lower affinity.

Key words : phencyclidine – thienylphencyclidine – MK-801 – higher affinity receptor– lower affinity receptor.

Full Text:

Untitled

References

Alburqueque, E. X., Tsai, M. C., Aronstam,R., Eldefrawi, A. T., and Eldefrawi, M. E.,1979, Sites of action of phencyclidine II : Interaction with the ionic channel of the nicotinic receptor. Mol.Pharmacol., 18, 167-178.

Anis, N. A., Berry, S. C., Burton, N. R., and Lodge ,D., 1983, The dissociative anesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurons by N-methyl-aspartate. Brit.J.Pharrnacol., 79, 565-576.

Blaustein, M. P., and Ickowicz, R. K.,1983, Phencyclidine in nanomolar concentrations binds to synaptosomes and block potassium channels. Proc.Natl.Acad.Scie.USA, 80, 3855-3859.

Chaudieu, I., Chicheportiche, M., Vignon, J., E l, Harfi, M., Kamenka, J. M., and Vignon, J., 1987, Recherche d’une correlation entre les sites marques a la 3H-PCP et la 3H-TCP dans le SNC de rat. Eur.J.Med.Chem.

Chicheportiche, R., Agid, Y., Chaudieu, I., Gusdinar, T., Agid, J., Journot, L., Kamenka, J. M., and Vignon, J., 1987, The multiple binding sites of 3H-PCP and 3H-TCP in the rat and human CNS. in : Sigma and phencyclidine-like compounds as molecular probes in biology. Domino, E.F. and Kamenka, J. M., Ed. NPP Book Ann Arbor, Michigan.

Clineschmidt, B. V., Martin, G. E., and Buntting, P. R., 1982, Anticonvulsant activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine (MK-801), a substance with potent anticonvulsant central sympathomimetic and apparent anxiolytic properties. Drug Dev.Res., 2, 123-134.

Gundlech, A. L., Largent, B. L., and Snyder, S. H.,1985, Phencyclidine and sigma opiate receptors in brain : Biochemical and autoradiographical differentiation. Eur.J. Pharmacol., 113, 465-466.

Lodge, D., and Johnston, G. A. R.,1985, Effect of ketamine on amino acid evoked release of acetylcholine from rat cerebral cortex in vitro, Neurosci.Lett., 56, 371-375. Quirion, R., Hammer, R. P., Jr., Herkenham, M., and Pert, C. B.,1981, Phencyclidine (angel dust) sigma opiate receptor : Visualization by tritium sensitive film. Proc.Natl.Acad. Sci. USA., 78, 5881-5885.

Tourneur,y., Romey, G., and Ladzunski, M.,1982, Phencyclidine blockade of sodium and potassium channel in neuroblastoma cells. Brain Research, 245, 154-158.

Vignon, J., Chicheportiche, R., Chicheportiche, M., Kamenka, J. M., Geneste, P., and Ladzunski, M., 1983, 3H-TCP : A new tool with high affinity for the PCP receptor in rat brain. Brain Research, 280, 194-197.

Vignon, J., and Ladzunski, M.,1984, Structure-function relationships in the inhibition of synaptosomal dopamine uptake by phencyclidine and analogues. Biochem.Pharma-col., 33, 700-702.

Vignon, J., Privat, A., Chaudieu, I., Thierry, A., Kamenka, J. M., and Chicheportiche, R., 1986, 3H-thienyl- phencyclidine (3H-TCP) binds to two different sites in rat brain. Localization by radioautographic and biochemical techniques. Brain Research, 378, 133-141.

Vincent, J. P., Kartalowski, B., Geneste, P., Kamenka, J. M., and Ladzunski, M., 1979, Interaction of phencyclidine (angel dust) with a specific receptor in rat brain membranes. Proc.Natl.Acad.Sci.USA, 76, 4678-4682.

Zukin, E., Kemp, J., Priestley, T., Knight, A., Woodruff, G., and Iversen, L, 1979, The anticonvulsivant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc.Natl.Acad. Sci.USA, 76, 5372-5376.

Zukin, R. S., and Zukin, S. R., 1981, Demonstration of 3H-cyclazocine binding to multiple opiate receptor sites. Mol.Pharmacol., 20, 246-254.

DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp190-198