1-ISOAMYL-3-ISOBUTYLXANTHINE - REMARKABLY POTENT AGENT FOR THE POTENTIATION OF NOREPINEPHRINE, HISTAMINE, AND ADENOSINE-ELICITED ACCUMULATIONS OF CYCLIC-AMP IN BRAIN-SLICES

被引：17

作者：

SMELLIE, FW ^{[1
]}

DALY, JW ^{[1
]}

WELLS, JN ^{[1
]}

机构：

[1] VANDERBILT UNIV,DEPT PHARMACOL,NASHVILLE,TN 37231

来源：

LIFE SCIENCES | 1979年 / 25卷 / 22期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/0024-3205(79)90613-1

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

1-Isoamyl-3-isobutylxanthine (EC50 t 5 μM) potentiates by 2 to 6-fold the accumulations of cyclic AMP elicited in guinea pig cerebral cortical slices by norepinephrine, histamine, and adenosine. In addition, the xanthine derivative causes a 2 to 3-fold elevation of basal levels of cyclic AMP. 1-Isoamyl-3-isobutylxanthine has no effect on accumulations of cyclic AMP elicited by histamine or adenosine in the presence of a potent phosphodiesterase inhibitor, ZK 62771. The xanthine derivative retards the disappearance of cyclic AMP after a prior stimulation by adenosine. The results indicate that 1-isoamyl-3-isobutylxanthine is an extremely potent and effective inhibitor of phosphodiesterases involved in the regulation of cyclic AMP levels in guinea pig cerebral cortical slices. The 1-benzyl, 1-isoamyl, and 1-isobutyl derivatives of 3-isobutylxanthine potentiate the accumulation of cyclic AMP elicited by adenosine, while the 1-methyl derivative and 1-isoamyl-3-methylxanthine are inhibitory undoubtedly because of blockade of adenosine-receptors by these compounds. Xanthines with bulky 1- and 3- substituents appear to be relatively weak adenosine-antagonists and relatively specific and potent agents for inhibition of phosphodiesterases involved in cyclic AMP metabolism in brain tissue. © 1979.

引用

页码：1917 / 1924

页数：8

共 16 条

[1]

BEAVO JA, 1970, MOL PHARMACOL, V6, P597

[2] INHIBITION OF SEPARATED FORMS OF PHOSPHODIESTERASES FROM PIG CORONARY-ARTERIES BY URACILS AND BY 7-SUBSTITUTED DERIVATIVES OF 1-METHYL-3-ISOBUTYLXANTHINE [J].