Studies on the N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) receptor in HIT T-15 cells. Displacement of [3H]glibenclamide

Tomonobu Fujita, Yoshiko Seto, Nobuo Kondo, Ryuichi Kato

研究成果: Article

23 引用 (Scopus)

抄録

A-4166 is a new type of oral hypoglycemic agent that does not contain a sulfonylurea moiety. To clarify the mechanism of insulin secretion by A-4166, a specific receptor for A-4166 was investigated in a hamster pancreatic β cell line (HIT T-15 ), using [3H]A-4166 or [3H]glibenclamide as a ligand. The saturation binding of [3H]A-4166 to HIT cell membranes was not observed up to 10 μM. In the displacement study, unlabeled A-4166 inhibited [3H]A-4166 binding to HIT cell membranes, but glibenclamide did not. On the other hand, A-4166 inhibited [3H]glibenclamide binding to the sulfonylurea receptor (K(i) = 248 nM). A-4166 inhibited 86Rb efflux from HIT cells (IC50 = 350 nM). The EC50 for insulin secretion by A-4166 was 20 μM in HIT cells when they were incubated for 30 min in Krebs-Ringer bicarbonate buffer containing 16 mM HEPES supplemented with 5 mg/mL BSA in the absence of glucose. These data demonstrate the possibility of the presence of two kinds of binding sites for A-4166: one of them is the sulfonylurea receptor, and the other might be a binding site specific for A-4166.

元の言語English
ページ(範囲)407-411
ページ数5
ジャーナルBiochemical Pharmacology
52
発行部数3
DOI
出版物ステータスPublished - 1996 8 9

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nateglinide
Glyburide
Phenylalanine
Sulfonylurea Receptors
Cell membranes
Binding Sites
Insulin
HEPES
Bicarbonates
Hypoglycemic Agents
Buffers
Cells
Ligands
Glucose
Cell Membrane

ASJC Scopus subject areas

  • Pharmacology

これを引用

Studies on the N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) receptor in HIT T-15 cells. Displacement of [3H]glibenclamide. / Fujita, Tomonobu; Seto, Yoshiko; Kondo, Nobuo; Kato, Ryuichi.

:: Biochemical Pharmacology, 巻 52, 番号 3, 09.08.1996, p. 407-411.

研究成果: Article

Fujita, Tomonobu ; Seto, Yoshiko ; Kondo, Nobuo ; Kato, Ryuichi. / Studies on the N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) receptor in HIT T-15 cells. Displacement of [3H]glibenclamide. :: Biochemical Pharmacology. 1996 ; 巻 52, 番号 3. pp. 407-411.
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