COMMON PHARMACOLOGICAL AND PHYSICOCHEMICAL PROPERTIES OF 5-HT3 BINDING-SITES IN THE RAT CEREBRAL-CORTEX AND NG 108-15 CLONAL CELLS

被引：74

作者：

BOLANOS, FJ ^{[1
]}

SCHECHTER, LE ^{[1
]}

MIQUEL, MC ^{[1
]}

EMERIT, MB ^{[1
]}

RUMIGNY, JF ^{[1
]}

HAMON, M ^{[1
]}

GOZLAN, H ^{[1
]}

机构：

[1] CTR RECH DELALANDE,F-92500 RUEIL MALMAISON,FRANCE

来源：

BIOCHEMICAL PHARMACOLOGY | 1990年 / 40卷 / 07期

关键词：

D O I：

10.1016/0006-2952(90)90452-Q

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

On account of the postulated existence of 5-HT3 receptor subtypes, the respective physicochemical and pharmacological properties of specific binding sites for the potent 5-HT3 antagonist [3H]zacopride were compared using membranes from the rat posterior cortex or neuroblastoma-glioma NG 108-15 clonal cells. In both membrane preparations, [3H]zacopride bound to a single class of specific sites with a Kd close to 0.5 nM. However, the Bmax value in NG 108-15 cell membranes (970 ± 194 mol/ mg protein) was approximately 50 times larger than that in cortical membranes (19 ± 2 mol/mg protein). The specific binding of [3H]zacopride was equally affected by temperature, pH and molarity of the assay medium, and equally insensitive to thiol- and disulfide-reagents (N-ethylmaleimide, p-chloro-mercuribenzene sulfonic acid, dithiothreitol) and GTP in cortical as well as NG 108-15 cell membranes. Determination of the molecular size of [3H]zacopride specific binding sites by radiation inactivation yielded values close to 35 kDa for both membrane preparations. Finally, a highly significant positive correlation (r = 0.979) was found between the respective pKi values of 34 different drugs for their inhibition of [3H]zacopride specific binding to cortical or NG 108-15 cell membranes. Among them, the most potent was S(-)zacopride (pKi = 9.55), followed by BRL 43964, ICS 205-930, quipazine, R(+)zacopride, GR 38032F and MDL 72222. Atyplcal antidepressants (mianserin, amoxapine) and neuroleptics (clotiapine, loxapine and clozapine) were active in rather low concentrations (pKi < 6.5), suggesting that recognition of 5-HT3 sites might be relevant to part of the in vivo effects of these drugs. Such identical physico-chemical and pharmacological properties of [3H]zacopride specific binding in cortical and NG 108-15 cell membranes strongly suggest that the same 5-HT3 receptor (subtype ?) exists in these two preparations. © 1990.

引用

页码：1541 / 1550

页数：10

共 42 条

[1] DIFFERENTIAL EFFECT OF TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS ON THE SUPPRESSANT ACTION OF 2-METHYLSEROTONIN ON MEDIAL PREFRONTAL CORTICAL-CELLS - A MICROIONTOPHORETIC STUDY [J].