Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: Implications for stimulus-response coupling of insulin release

Shepherd, R. M. and Hashmi, M. N. and Kane, C. and Squires, Paul and Dunne, M. J. (1996) Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: Implications for stimulus-response coupling of insulin release. British Journal of Pharmacology, 119 (5). pp. 911-916. ISSN 0007-1188

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Item Type:Article
Item Status:Live Archive

Abstract

1. Microfluorimetry techniques with fura-2 were used to characterize the effects of efaroxan (200 μM), phentolamine (200-500 μM) and idazoxan (200-500 μM) on the intracellular free Ca2+ concentration (Ca2+(i)) in mouse isolated islets of Langerhans. 2. The imidazoline receptor agonists efaroxan and phentolamine consistently elevated cytosolic Ca2+ by mechanisms that were dependent upon Ca2+ influx across the plasma membrane; there was no rise in Ca2+(i) when Ca2+ was removed from outside of the islets and diazoxide (100-250 μM) attenuated the responses. 3. Modulation of cytosolic Ca2+(i) by efaroxan and phentolamine was augmented by glucose (5-10 mM) which both potentiated the magnitude of the response and reduced the onset time of imidazoline-induced rises in Ca2+(i). 4. Efaroxan- and phentolamine-evoked increases in Ca2+(i) were unaffected by overnight pretreatment of islets with the imidazolines. Idazoxan failed to increase Ca2+(i) under any experimental condition tested. 5. The putative endogenous ligand of imidazoline receptors, agmatine (1 μM-1 mM), blocked K(ATP) channels in isolated patches of β-cell membrane, but effects upon Ca2+(i) could not be further investigated since agmatine disrupts fura-2 fluorescence. 6. In conclusion, the present study shows that imidazolines will evoke rises in Ca2+(i) in intact islets, and this provides an explanation to account for the previously described effects of imidazolines on K(ATP) channels, the cell membrane potential and insulin secretion in pancreatic β-cells.

Keywords:adenosine triphosphatase (potassium), agmatine, calcium ion, diazoxide, efaroxan, fura 2, idazoxan, imidazoline derivative, imidazoline receptor, insulin, phentolamine, phentolamine mesylate, animal tissue, article, calcium cell level, calcium transport, controlled study, drug mechanism, insulin release, microfluorometry, mouse, nonhuman, pancreas islet, priority journal, Adrenergic alpha-Antagonists, Animals, Benzofurans, Calcium, Cytosol, Down-Regulation, Glucose, Imidazoles, Islets of Langerhans, Mice, Receptors, Drug, Signal Transduction
Subjects:B Subjects allied to Medicine > B210 Pharmacology
Divisions:College of Science > School of Life Sciences
ID Code:14469
Deposited On:11 Jul 2014 11:35

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