Calmodulin and insulin secretion: use of naphthalenesulfonamide compounds
| Autor: | G. C. Yaney, Geoffrey W. G. Sharp |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty Calmodulin Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment chemistry.chemical_element In Vitro Techniques Calcium Cell Line Islets of Langerhans Physiology (medical) Internal medicine Insulin Secretion medicine Animals Insulin Secretion Insulin secretion Pancreatic hormone Sulfonamides biology Binding protein Rats Inbred Strains 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester In vitro Rats Pancreatic Neoplasms Kinetics Endocrinology chemistry biology.protein Insulinoma Fura-2 |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 259:E856-E864 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.1990.259.6.e856 |
| Popis: | Studies have been performed on the involvement of calmodulin in the control of stimulated insulin secretion. The W-compounds, which are sulfonamide-derivative calmodulin inhibitors, were used in analogue pairs to control for hydrophobic and nonspecific effects. N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide HCl (W-13) inhibited glucose-stimulated insulin secretion from rat pancreatic islets over the concentration range appropriate for an action involving calmodulin. The control compound N-(4-aminobutyl)-2-naphthalenesulfonamide HCl (W-12) inhibited slightly only at higher concentrations. Similar differential inhibition by the analogue pairs was found using W-13 and W-12 and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide HCl (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide HCl (W-5) against depolarization-induced insulin secretion in the RINm5F clonal beta-cell line. A sufficient explanation for the inhibition of insulin release was found in the differential inhibition of depolarization-induced Ca2+ uptake, which located the action of the W-compounds at the voltage-dependent Ca2+ channels. These data suggest an action of the W-compounds at a point before elevation of intracellular Ca2+ concentration [( Ca2+]i) in stimulus-secretion coupling. In subsequent studies, with the voltage-dependent Ca2(+)-channel agonist BAY K 8644, which increases Ca2+ uptake and the rate of insulin secretion, it was demonstrated that the W-compounds had no effect on the stimulation of 45Ca2+ uptake or insulin secretion. Thus the W-compounds inhibit stimulus-secretion coupling before the elevation of [Ca2+]i but appear to have no action subsequently. These data cast doubt on the hypothesis that calmodulin is involved in stimulus-secretion coupling. |
| Databáze: | OpenAIRE |
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