BINDING OF THE MUSCARINE RECEPTOR ANTAGONIST HEPTANE-1,7-BIS(DIMETHYL-3'-PHTHALIMIDOPROPYL)AMMONIUM BROMIDE AT CHOLINOCEPTOR SITES

被引:18
作者
CHRISTOPOULOS, A
LOIACONO, R
MITCHELSON, F
机构
[1] MONASH UNIV, VICTORIAN COLL PHARM, SCH PHARMACOL, 381 ROYAL PARADE, PARKVILLE, VIC 3052, AUSTRALIA
[2] MONASH UNIV, DEPT PHARMACOL, CLAYTON, VIC 3168, AUSTRALIA
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1993年 / 246卷 / 01期
关键词
MUSCARINE RECEPTOR ANTAGONIST; CEREBRAL CORTEX; CHOLINOCEPTOR;
D O I
10.1016/0922-4106(93)90002-Q
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3'-phthalimidopropyl)-ammonium bromide (C-7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[H-3]nicotine, [H-3]pirenzepine and (-)-[H-3]quinuclidinyl benzilate ([H-3]QNB) in both central and peripheral tissues. C-7/3-phth displayed an affinity for muscarine M2 receptors in rat atria (70.1 nM) which was 1.6-fold greater than for putative M4 receptors in rabbit lung, and 4- to 5-fold greater than for M1 receptors in rat cerebral cortex. Its affinity for nicotine receptors in the cortex was low, being 808-fold lower than its affinity for the M2 receptor. Although the displacement of (-)-[H-3]nicotine and [H-3]pirenzepine binding in rat cortex by C-7/3-phth was best described in terms of one-site modelling, low Hill coefficients were observed with C-7/3-phth in displacement studies using [H-3]QNB in this tissue. The possibility of allosteric interactions or multiple receptor subtype interactions is discussed.
引用
收藏
页码:1 / 8
页数:8
相关论文
共 40 条
  • [11] GIRALDO E, 1988, J PHARMACOL EXP THER, V244, P1016
  • [12] DISTRIBUTION OF MUSCARINIC RECEPTOR SUBTYPES IN RAT-BRAIN AS DETERMINED IN BINDING-STUDIES WITH AF-DX 116 AND PIRENZEPINE
    GIRALDO, E
    HAMMER, R
    LADINSKY, H
    [J]. LIFE SCIENCES, 1987, 40 (09) : 833 - 840
  • [13] BINDING PROFILE OF A NOVEL CARDIOSELECTIVE MUSCARINE RECEPTOR ANTAGONIST, AF-DX 116, TO MEMBRANES OF PERIPHERAL-TISSUES AND BRAIN IN THE RAT
    HAMMER, R
    GIRALDO, E
    SCHIAVI, GB
    MONFERINI, E
    LADINSKY, H
    [J]. LIFE SCIENCES, 1986, 38 (18) : 1653 - 1662
  • [14] PIRENZEPINE DISTINGUISHES BETWEEN DIFFERENT SUBCLASSES OF MUSCARINIC RECEPTORS
    HAMMER, R
    BERRIE, CP
    BIRDSALL, NJM
    BURGEN, ASV
    HULME, EC
    [J]. NATURE, 1980, 283 (5742) : 90 - 92
  • [15] THE HUMAN ASTROCYTOMA CELL-LINE 1321-N1 CONTAINS M2-GLANDULAR TYPE MUSCARINIC RECEPTORS LINKED TO PHOSPHOINOSITIDE TURNOVER
    KUNYSZ, EA
    MICHEL, AD
    WHITING, RL
    WOODS, K
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1989, 96 (02) : 271 - 278
  • [16] LAZARENO S, 1990, MOL PHARMACOL, V38, P805
  • [17] ANOMALOUS BINDING OF [H-3] N-METHYLSCOPOLAMINE TO RAT-BRAIN MUSCARINIC RECEPTORS
    LEE, JH
    ELFAKAHANY, EE
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1985, 110 (02) : 263 - 266
  • [18] LEE NH, 1991, J PHARMACOL EXP THER, V256, P468
  • [19] LEE NH, 1989, J PHARMACOL EXP THER, V251, P992
  • [20] INTERACTION OF THE HEXAMETHONIUM DERIVATIVE-W84, AN ALLOSTERIC EFFECTOR AT MUSCARINIC CHOLINOCEPTORS, WITH RAT-BRAIN NICOTINIC BINDING-SITES
    LEITHAUSER, F
    MOHR, K
    STASCHEN, CM
    [J]. PHARMACOLOGY & TOXICOLOGY, 1990, 67 (04): : 317 - 321