[H-3] TRICYCLOPINATE BINDING TO BRAIN MUSCARINIC ACETYLCHOLINE-RECEPTORS - A COMPARISON WITH [H-3] QUINUCLIDINYL BENZILATE

Authors
Citation
Zg. Gao et Cg. Liu, [H-3] TRICYCLOPINATE BINDING TO BRAIN MUSCARINIC ACETYLCHOLINE-RECEPTORS - A COMPARISON WITH [H-3] QUINUCLIDINYL BENZILATE, Pharmacological research, 33(4-5), 1996, pp. 283-289
Citations number
20
Categorie Soggetti
Pharmacology & Pharmacy
Journal title
ISSN journal
10436618
Volume
33
Issue
4-5
Year of publication
1996
Pages
283 - 289
Database
ISI
SICI code
1043-6618(1996)33:4-5<283:[TBTBM>2.0.ZU;2-M
Abstract
The purpose of our study was to investigate the binding characteristic s of a newly synthesized compound, tricyclopinate, at muscarinic acety lcholine receptors from rat cerebral cortex. This was achieved through the use of radiolabelled quinuclidinyl benzilate and radiolabelled tr icyclopinate. Our data demonstrated that the saturation binding parame ters of [H-3]tricyclopinate (K-d=0.10 nM, B-max=1056 fmol mg(-1)) were almost identical to those of [H-3]quinuclidinyl benzilate (K-d=0.11 n M, B-max=1022 fmol mg(-1)); both ligands fit a one site model of recep tor-ligand interaction. Concentration-inhibition curves were used to d etermine K-i values for four antimuscarinic compounds. The rank order of potencies of the antagonists for displacement of the two ligands wa s: tricyclopinate=quinuclidinyl benzilate>atropine> pirenzepine. The c ompetition binding parameters of [H-3]tricyclopinate were similar to t hose of [H-3]quinuclidinyl benzilate. The associate rate constants (K- 1) were 0.25 and 0.21 nM(-1) min(-1) for [H-3]tricyclopinate and [H-3] quinuclidinyl benzilate, respectively. The dissociation of bound [H-3] tricyclopinate from central muscarinic acetylcholine receptors was com plete and was modified by the allosteric agent, gallamine. By comparis on, only half of the bound [H-3]quinuclidinyl benzilate was dissociate d from muscarinic acetylcholine receptors and the dissociation of boun d [H-3]quinuclidinyl benzilate was not modified by gallamine. The diss ociation rate constants (K--1) were 0.0325 and 0.0072 min(-1) for [H-3 ]tricyclopinate and [H-3]quinuclidinyl benzilate, respectively. These results showed that the two ligands have different binding characteris tics to muscarinic acetylcholine receptors. [H-3]tricyclopinate should be very useful for further study of central muscarinic acetylcholine receptors; it might complement the use of [H-3]N-methylscopolamine and [H-3]quinuclidinyl benzilate in the study of muscarinic acetylcholine receptors. (C) 1996 The Italian Pharmacological Society.