D-optimal design applied to binding saturation curves of an enkephalin analog in rat brain

Journal Article · Fri Jan 01 00:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90466-3· OSTI ID:5515903

Verotta, D; Petrillo, P; La Regina, A; Rocchetti, M; Tavani, A

The D-optimal design, a minimal sample design that minimizes the volume of the joint confidence region for the parameters, was used to evaluate binding parameters in a saturation curve with a view to reducing the number of experimental points without loosing accuracy in binding parameter estimates. Binding saturation experiments were performed in rat brain crude membrane preparations with the opioid ..mu..-selective ligand (/sup 3/H)-(D-Ala/sup 2/, MePhe/sup 4/, Gly-ol/sup 5/)enkephalin (DAGO), using a sequential procedure. The first experiment consisted of a wide-range saturation curve, which confirmed that (/sup 3/H)-DAGO binds only one class of specific sites and non-specific sites, and gave information on the experimental range and a first estimate of binding affinity (K/sub a/), capacity (B/sub max/) and non-specific constant (k). On this basis the D-optimal design was computed and sequential experiments were performed each covering a wide-range traditional saturation curve, the D-optimal design and a splitting of the D-optimal design with the addition of 2 points (+/- 15% of the central point). No appreciable differences were obtained with these designs in parameter estimates and their accuracy. Thus, sequential experiments based on D-optimal design seem a valid method for accurate determination of binding parameters, using far fewer points with no loss in parameter estimation accuracy. 25 references, 2 figures, 3 tables.

• Research Organization: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
• OSTI ID: 5515903
• Journal Information: Life Sci.; (United States), Vol. 42:6
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BIOCHEMICAL REACTION KINETICS
MATHEMATICAL MODELS
ENKEPHALINS
RECEPTORS
BRAIN
CELL MEMBRANES
EXPERIMENTAL DATA
LIGANDS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DATA
DRUGS
ENDORPHINS
INFORMATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques