Bromoacetylated analogue of cyanopindolol: an irreversible antagonist at rat beta-adrenoceptors
A high affinity, chemically reactive cyanopindolol derivative N/sup 8/-bromoacetyl-N/sup 1/-3'-(2-cyano-4-indolyloxy)-2'-hydroxypropyl-(Z)-1,8-diamino-p-menthane (Br-CYP) was synthesized and its interaction with ..beta..-adrenoceptors characterized. Studies with rat heart, lung, brain and red blood cell membranes indicated that the compound displaced /sup 3/H-dihydroalprenolol (/sup 3/H-DHA) from ..beta..-adrenoceptors with IC/sub 50/ values in the nanomolar range. The concentration of functional ..beta..-adrenoceptors in membranes was markedly reduced when membranes were preincubated with Br-CYP and then extensively washed prior to assay. (+/-)Alprenolol and (-)isoproterenol, but not (+)isoproterenol, when included in the preincubation prevented this reduction in binding sites by Br-CYP. Br-CYP was active in vivo when injected intraperitoneally into rats. A dose of 10 ..mu..g/kg reduced the concentration of binding sites in membranes from heart by 30%, lung by 36%, and RBC by 70%, but did not affect sites on brain membranes 16 hours after injection. Higher doses blocked virtually all the /sup 3/H-DHA binding sites in the peripheral organs studied. These results suggest that Br-CYP may be a useful compound for in vivo studies of the biochemistry and pharmacology of ..beta..-adrenergic systems. 27 references, 4 figures, 3 tables.
- Research Organization:
- National Institute on Aging-GRC, Baltimore, MD
- OSTI ID:
- 6501684
- Journal Information:
- Life Sci.; (United States), Vol. 41:1
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effects of chronic isoproterenol administration of. beta. /sub 1/-adrenoceptors and growth of pancreas of young and adult rats
Dual aminergic regulation of central beta adrenoceptors. Effect of atypical antidepressants and 5-hydroxytryptophan
Related Subjects
SYMPATHOLYTICS
BIOCHEMICAL REACTION KINETICS
CHEMICAL PREPARATION
SYMPATHOMIMETICS
RECEPTORS
BRAIN
CELL MEMBRANES
ERYTHROCYTES
EXPERIMENTAL DATA
HEART
LUNGS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DATA
DRUGS
INFORMATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques