Tolbutamide and glyburide differ in effectiveness to displace α- and β-adrenergic radioligands in pancreatic islet cells and membranes

• Published in: Diabetes (New York, N.Y.) Vol. 33; no. 5; pp. 499 - 503
• Main Authors: CHERKSEY, B, ALTSZULER, N
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.05.1984
• Subjects: Alprenolol - analogs & derivatives; Animals; Biological and medical sciences; Cell Membrane - metabolism; Clonidine - metabolism; Dihydroalprenolol - metabolism; Epinephrine - pharmacology; Glyburide - pharmacology; Hormones. Endocrine system; Islets of Langerhans - metabolism; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Receptors, Adrenergic - drug effects; Receptors, Adrenergic, alpha - drug effects; Receptors, Adrenergic, beta - drug effects; Tolbutamide - pharmacology; Rat; Rodentia; In vitro; Biological activity; Radiochemical method; Vertebrata; Hypoglycemic agent; Mammalia; Α-Adrenergic receptor; Plasma membrane; Sulfonylureas; Langerhansian islet; Cell; Comparative study
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.33.5.499

Previous in vivo findings indicated that alpha-adrenergic blocking agents enhanced tolbutamide-induced insulin secretion, whereas beta-blockade attenuated it. In the present study, the interaction of tolbutamide and glyburide with the rat islet adrenergic receptors is examined directly by determining the effectiveness of these drugs to displace the specific alpha- and beta-adrenergic radioligands, [3H]-clonidine and [3H]-dihydroalprenolol (DHA). It was found that both tolbutamide and glyburide had affinity constants for the adrenergic receptors that were similar to those for the natural receptor ligands and powerful antagonists. Tolbutamide displaced both alpha- and beta-radioligands but had a higher affinity at the beta-receptor. Glyburide also displaced radioligands from both types of receptors but had a higher affinity for the alpha-receptor. This study suggests that these two sulfonylurea hypoglycemic agents may affect insulin secretion by different mechanisms.