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- Title
Effect of purinergic agonists and antagonists on insulin secretion from INS-1 cells (insulinoma cell line) and rat pancreatic islets.
- Authors
Verspohl, E.J.; Johannwille, B.; Waheed, A.; Neye, H.
- Abstract
The effects of purinergic agonists on insulin release are controversial in the literature. In our studies (mainly using INS-1 cells, but also using rat pancreatic islets), ATP had a dual effect on insulin release depending on the ATP concentration: increasing insulin release (EC 50 ≈ 0.0032 μM) and inhibiting insulin release (EC 50 ≈ 0.32 μM) at both 5.6 and 8.3 mM glucose. This is compatible with the view that either two different receptors are involved, or the cells desensitize and (or) the effect of an inhibitory degradation product such as adenosine (ectonucleotidase effect) emerges. The same dual effects of ATP on insulin release were obtained using rat pancreatic islets instead of INS-1 cells. ADPβS, which is less degradable than ATP and rather specific for P 2Y1 receptors, had a dual effect on insulin release at 8.3 mM glucose: stimulatory (EC 50 ≈ 0.02 μM) and inhibitory (EC 50 ≈ 0.32 μM). The effectiveness of this compound indicates the possible involvement of a P[sub2Y1] receptor. 2-Methylthio-ATP exhibited an insulinotropic effect at very high concentrations (EC 50 ≈ 15 μM at 8.3 mM glucose). This indicated that distinct P[sub2X] or the P[sub2Y1] receptor may be involved in these insulin-secreting cells. UTP increased insulin release (EC 50 ≈ 2 μM) very weakly, indicating that a P[sub2U] receptor (P[sub2X3] or possibly a P[sub2Y2] or P[sub2Y4]) are not likely to be involved. Suramin (50 μM) antagonized the insulinotropic effect of ATP (0.01 μM) and UTP (0.32 μM). Since suramin is not selective, the data indicated that various P[sub2X] and P[sub2Y] receptors may be involved. PPADS (100 mM), a P[sub2X] and P[sub2Y1,4,6] receptor antagonist, was ineffective using either low or high concentrations of ATP...
- Subjects
INSULIN; HORMONES; PANCREATIC secretions; HYPOGLYCEMIC agents; CELL receptors; BINDING sites
- Publication
Canadian Journal of Physiology & Pharmacology, 2002, Vol 80, Issue 6, p562
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/y02-079