Abstract

This project tests a number of predictions of the hypothesis that adenosine is a physiological regulator of coronary flow and cardiac performance. These include the predictions that the purine dipole moment and the stereoselective interaction of exocyclic purine substituents with specialized regions of the coronary adenosine receptor determine the vasoactivity of adenosines and antagonism by theophyllines. These studies employ C2 and C6 substituted nebularines and N1 and N3 alkylxanthines. Tests of the hypothesis that the anti-N-g+ conformer of adenosine binds to the receptor employs 2 feet-substituted 2 feet-deoxyadenosines. Studies testing the hypothesis that there are regional differences in the type of adenosine R receptors employ enzymatically dispersed cardiocytes and adenosine analogs covalently linked to dextrans to prevent penetration into cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030391-02
Application #
3341415
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-02-01
Project End
1987-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of South Florida
Department
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612

  Publications

Niiya, K; Uchida, S; Tsuji, T et al. (1994) Glibenclamide reduces the coronary vasoactivity of adenosine receptor agonists. J Pharmacol Exp Ther 271:14-9
Niiya, K; Jacobson, K A; Silvia, S K et al. (1993) Covalent binding of a selective agonist irreversibly activates guinea pig coronary artery A2 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 347:521-6
Niiya, K; Olsson, R A; Thompson, R D et al. (1992) 2-(N'-alkylidenehydrazino)adenosines: potent and selective coronary vasodilators. J Med Chem 35:4557-61
Ueeda, M; Silvia, S K; Olsson, R A (1992) Nitric oxide modulates coronary autoregulation in the guinea pig. Circ Res 70:1296-303
Niiya, K; Thompson, R D; Silvia, S K et al. (1992) 2-(N'-aralkylidenehydrazino)adenosines: potent and selective coronary vasodilators. J Med Chem 35:4562-6
Thompson, R D; Secunda, S; Daly, J W et al. (1991) Activity of N6-substituted 2-chloroadenosines at A1 and A2 adenosine receptors. J Med Chem 34:3388-90
Ueeda, M; Thompson, R D; Arroyo, L H et al. (1991) 2-Alkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor. J Med Chem 34:1334-9
Thompson, R D; Secunda, S; Daly, J W et al. (1991) N6,9-disubstituted adenines: potent, selective antagonists at the A1 adenosine receptor. J Med Chem 34:2877-82
Olsson, R A; Pearson, J D (1990) Cardiovascular purinoceptors. Physiol Rev 70:761-845
Lohse, M J; Klotz, K N; Lindenborn-Fotinos, J et al. (1987) 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX)--a selective high affinity antagonist radioligand for A1 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 336:204-10

Showing the most recent 10 out of 19 publications