Ca. Alter et al., U-73122 DOES NOT SPECIFICALLY INHIBIT PHOSPHOLIPASE-C IN RAT PANCREATIC-ISLETS AND INSULIN-SECRETING BETA-CELL LINES, Life sciences, 54(8), 1994, pp. 107-112
Citations number
21
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Phospholipase C is activated in insulin secretion by islets of Langerh
ans and insulin-secreting beta-cells such as RINm5F and beta-TCS. We h
ave examined the effects of the aminosteroid U-73122, a phospholipase
C inhibitor, on insulin secretion and phospholipase C activation. U-73
122 slightly inhibited glucose-induced insulin secretion from islets,
but this effect was not specific since the structural ''inactive'' ana
logue U-73343 also inhibited insulin secretion. Likewise, in RINm5F ce
lls, U-73122 did not inhibit glyceraldehyde-induced insulin secretion.
Phospholipase C activity was assessed as the accumulation of inositol
-1,4,5-trisphosphate (Ins(1,4,5)P-3) measured with a competitive bindi
ng assay: U-73122 failed to inhibit glucose-induced increase in Ins(1,
4,5)P-3. Similarly, when the effects of U-73122 and U-73343 were measu
red on [H-3]phosphatidylinositol hydrolysis of islets, both compounds
caused a slight, non-specific inhibition of phospholipase C activity.
These observations suggest that U-73122 does not specifically inhibit
phospholipase C in insulin-secreting cells.