Back to Search Start Over

Effect of Ergot Alkaloids on Sulfonylurea-Stimulated Insulin Secretion in Dogs

Authors :
A. Kerekes
Z. Policova
A. Sirek
O.V. Sirek
Source :
Pharmacology. 15:259-267
Publication Year :
1977
Publisher :
S. Karger AG, 1977.

Abstract

The insulinogenic response to a standard i.v. dose of a sulfonylurea can be markedly augmented in normal, conscious dogs if they are given 30 min earlier a single i.v. dose of dihydroergotamine (DHE). Since the parent substance ergotamine posssed no such amplifying properties, further experiments were conducted to clarify the essential structural requirements that have to be fulfilled for an ergot alkaloid to act as an amplifier of sulfonylurea-stimulated insulin secretion. Amine alkaloids ergonovine, dihydroergonovone and dihydromethylergonovine had no amplifying potency, but the hydrogenated amino acid alkaloids dihydroergocornine, dihydroergocristine and dihydroergokryptine (Hydergine) were almost as potent amplifiers as was DHE. The data indicate that (a) DHE, Hydergine and by inference all hydrogenated amino acid alkaloids are potent amplifiers of sulfonylurea-stimulated insulin secretion; (b) saturation of the double bond at C9 and C10 of the lysergic acid moiety and the pressence of an amino acid side chain are essential structual requirements for an ergot alkaloid to function as an amplifier of the action of sulfonylureas; and (c) it appears that these compounds are acting chiefly by mechanisms other than alpha-adrenergic and serotonergic receptor blockade, perhaps as regulatory molecules inducing positive cooperative changes in integral proteins of the plasma membrane of beta cells.

Details

ISSN :
14230313 and 00317012
Volume :
15
Database :
OpenAIRE
Journal :
Pharmacology
Accession number :
edsair.doi.dedup.....7b77cb533cdc62cff25b434d17b8a2f2
Full Text :
https://doi.org/10.1159/000136697