High affinity ( sup 3 H)glibenclamide binding sites in rat neuronal and cardiac tissue: Localization and developmental characteristics

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6057813

Miller, J A; Velayo, N L; Dage, R C; Rampe, D ^[1]

---

1. Merrell Dow Research Institute, Cincinnati, OH (USA)

We examined the binding of the antidiabetic sulfonylurea (3H) glibenclamide to rat brain and heart membranes. High affinity binding was observed in adult rat forebrain (Kd = 137.3 pM, maximal binding site density = 91.8 fmol/mg of protein) and ventricle (Kd = 77.1 pM, maximal binding site density = 65.1 fmol/mg of protein). Binding site density increased approximately 250% in forebrain membranes during postnatal development but was constant in ventricular membranes. Quantitative autoradiography was used to examine the regional distribution of (3H) glibenclamide binding sites in sections from rat brain, spinal cord and heart. The greatest density of binding in adult brain was found in the substantia nigra and globus pallidus, whereas the other areas displayed heterogenous binding. In agreement with the membrane binding studies, 1-day-old rat brain had significantly fewer (3H)glibenclamide binding sites than adult brain. Additionally, the pattern of distribution of these sites was qualitatively different from that of the adult. In adult rat spinal cord, moderate binding densities were observed in spinal cord gray and displayed a rostral to caudal gradient. In adult rat heart, moderate binding densities were observed and the sites were distributed homogeneously. In conclusion, significant development of (3H)glibenclamide binding sites was seen in the brain but not the heart during postnatal maturation. Furthermore, a heterogeneous distribution of binding sites was observed in both the brain and spinal cord of adult rats.

• OSTI ID: 6057813
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 256:1; ISSN 0022-3565; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMAL CELLS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHEMICAL COMPOSITION
DISTRIBUTION
DRUGS
HEART
HYDROGEN COMPOUNDS
KINETICS
MEMBRANE PROTEINS
MEMBRANES
NERVE CELLS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RECEPTORS
SOMATIC CELLS
SPINAL CORD
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS