Our aim is to classify and characterize peripheral effector receptors for 5-hydroxytryptamine (5-HT). A functional (pharmacological) approach to the problem is taken using isolated tissues set-up in vitro. Initial studies will be done on the isolated perfused rat kidney, the isolated rat vas deferens, and the isolated perfused rat mesenteric arteries. Subsequent experiments will be done with rat isolated atria, caudal arteries, and saphenous veins. The experiments will focus on peripheral receptors for 5-HT at sympathetic neuroeffector junctions at both prejunctional and postjunctional sites. Quantitative pharmacological analysis will be done with competitive antagonists, irreversible antagonists and a range of 5-HT-like agonists. The determination of pA2 values for competitive antagonists, agonist potency ratios, affinities and relative efficacies will be determined and used to classify and characterize the receptors. Criteria for defining three separate groups of 5-HT receptors (""""""""5-HT1-like"""""""", 5-HT2, and 5-HT3) are given and will serve as the broad basis for receptor classification. The project represents a careful basic science pharmacological research investigation into receptor classification and characterization. Such research is a prerequisite for the full understanding of the biological and pathological effects of 5-HT and for the rational development of new serotonergic drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS024871-01
Application #
3409831
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Houston
Department
Type
Schools of Pharmacy
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77204