Species differences in structure‐activity relationships of adenosine agonists and xanthine antagonists at brain A1 adenosine receptors

FEBS Letters

Ayala, Cristina¹  Olssont, Ray O.²  Jacobson, Kenneth A.³  Kirk, Kenneth L.³  Shamim, Mah T.¹  Ukena, Dieter¹  Daly, John W.¹  Padgett, William L.¹ 

[1] Laboratory of Bioorganic Chemistry National Institute of Diabetes, and Digestive and Kidney diseases, National Institutes of Health, Bethesda, MD 20892 USA;Department of Internal Medicine, University of South Florida, College of Medicine, Tampa, FL 33612, USA;Laboratory of Chemistry, National Institute of Diabetes, and Digestive and Kidney diseases, National Institutes of Health, Bethesda, MD 20892 USA

关键词: Adenosine agonist Xanthine antagonist Adenosine receptor Structure-activity;   

DOI  :  10.1016/0014-5793(86)81096-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A series of 28 adenosine analogs and 17 xanthines has been assessed as inhibitors of binding of N ⁶-R-[³H]-phenylisopropyladenosine binding to A1 adenosine receptors in membranes from rat, calf, and guinea pig brain. Potencies of N ⁶-alkyl- and N ⁶-cycloalkyladenosines are similar in the different species. However, the presence of an aryl or heteroaryl moiety in the N ⁶ substituent results in marked species differences with certain such analogs being about 30-fold more potent at receptors in calf than in guinea pig brain. Potencies at receptors in rat brain are intermediate. Conversely, 2-chloroadenosine and 5'-N-ethylcarboxamido-adenosine are about 10-fold less potent at receptors in calf brain than in guinea pig brain. Potencies of xanthines, such as theophylline, caffeine and 1,3-dipropylxanthine are similar in the different species. However, the presence of an 8-phenyl or 8-cycloalkyl substituent results in marked species differences. For example, a xanthine amine conjugate of 1,3-dipropyl-8-phenylxanthine is 9-fold more potent at receptors in calf than in rat brain and 110-fold more potent in calf than in guinea pig brain. Such differences indicate that brain A1 adenosine receptors are not identical in recognition sites for either agonists or antagonists in different mammalian species.

【 授权许可】

Unknown