Characterization of some carbostyril congeners having novel beta-adrenoreceptor agonist properties
The interaction of two new derivatives of 8-hydroxy-carbostyril with the beta-adrenoreceptor system was partially characterized using isolated membranes, cultured cells, and animals. These carbostyril congeners contained an amino (Carbo-Am) or bromoacetamido (Carbo-Br) moiety in the para position of the phenyl ring. In rat reticulocyte membranes, binding studies under different conditions with ({sup 125}I)iodocyanopindolol revealed that Carbo-Br and Carbo-Am were 17 to 107-fold more potent that (-)isoproterenol Carbo-Am and Carbo-Br were 13.5 and 30-fold, respectively, more potent than (-)isoproterenol at stimulating adenylate cyclase activity, but exhibited the same intrinsic activity. Adenylate cyclase activation by Carbo-Br, Carbo-Am or (-)isoproterenol was blocked with concurrent addition of propranolol. If, however, propranolol was added 7 min into the assay, further cAMP production by Carbo-Br and Carbo-Am was unaffected while further cAMP production by (-)isoproterenol was immediately blocked. Both Carbo-Br and Carbo-Am induced a receptor loss that was blocked by nadolol. The tightly bound Carbo-Am could be partially dissociated by heat treatment whereas Carbo-Br could not.
- Research Organization:
- Florida Univ., Gainesville, FL (USA)
- OSTI ID:
- 7147250
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMP
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CHEMICAL COMPOSITION
CYCLASES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LYASES
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRIDINES
QUINOLINES
RADIOISOTOPES
RATS
RECEPTORS
RODENTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
VERTEBRATES