The original objective of this project is to characterize by pharmacological and biochemical methods the adrenergic receptors in selected sympathetically innervated tissues in order to improve our understanding of factors at the receptor level which regulate the responses of these tissues to various adrenergic drugs and to sympathetic nerve stimulation. Experiments will be carried out (1) to ascertain whether the simultaneous occurrence of more than one type of adrenergic beta-receptor in a single cell type is a common phenomenon; (2) to elucidate the factors which control the variable ratio of beta1-to beta2-type receptors in selected smooth muscle cells; (3) to reexamine whether postjunctional adrenergic alpha-receptors in different sympathetic effectors in the same species are all of a single type. Characterization of receptors responsible for mediating a specific response in a given isolated tissue will be carried out by determining with appropriate pharmacological procedures affinities and efficacies of selected agonists, and affinities of selected competitive antagonists. In addition, we shall apply radioactive ligand-binding techniques for quantification of one or more types of beta-receptors or alpha-receptors in selected tissues. In addition to the original objective, a new major objective is to elucidate the mechanism by which acetylcholine relaxes blood vessels. We have already demonstrated with isolated vessels that this relaxation is the result of acetylcholine acting on the muscarinic receptors of endothelial cells, which then are stimulated to produce and release a substance that relaxes the smooth muscle cells. Pharmacological and biochemical studies will be directed at determining the nature of released relaxing substance and the mechanism whereby it activates relaxation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL021860-27
Application #
3336642
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1977-12-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
27
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Furchgott, R F (1993) Introduction to EDRF research. J Cardiovasc Pharmacol 22 Suppl 7:S1-2
Jia, L; Furchgott, R F (1993) Inhibition by sulfhydryl compounds of vascular relaxation induced by nitric oxide and endothelium-derived relaxing factor. J Pharmacol Exp Ther 267:371-8
Khan, M T; Jothianandan, D; Matsunaga, K et al. (1992) Vasodilation induced by acetylcholine and by glyceryl trinitrate in rat aortic and mesenteric vasculature. J Vasc Res 29:20-8
Matsunaga, K; Furchgott, R F (1991) Responses of rabbit aorta to nitric oxide and superoxide generated by ultraviolet irradiation of solutions containing inorganic nitrite. J Pharmacol Exp Ther 259:1140-6
Furchgott, R F (1991) Endothelium-dependent relaxation, endothelium-derived relaxing factor and photorelaxation of blood vessels. Semin Perinatol 15:11-5
Furchgott, R F; Jothianandan, D (1991) Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 28:52-61
Furchgott, R F (1990) The 1989 Ulf von Euler lecture. Studies on endothelium-dependent vasodilation and the endothelium-derived relaxing factor. Acta Physiol Scand 139:257-70
Furchgott, R F; Vanhoutte, P M (1989) Endothelium-derived relaxing and contracting factors. FASEB J 3:2007-18
Matsunaga, K; Furchgott, R F (1989) Interactions of light and sodium nitrite in producing relaxation of rabbit aorta. J Pharmacol Exp Ther 248:687-95
Furchgott, R F; Carvalho, M H; Khan, M T et al. (1987) Evidence for endothelium-dependent vasodilation of resistance vessels by acetylcholine. Blood Vessels 24:145-9

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