U-73122 does not specifically inhibit phospholipase C in rat pancreatic islets and insulin-secreting beta-cell lines.
Phospholipase C is activated in insulin secretion by islets of Langerhans and insulin-secreting beta-cells such as RINm5F and beta-TC3. We have examined the effects of the aminosteroid U-73122, a phospholipase C inhibitor, on insulin secretion and phospholipase C activation. U-73122 slightly inhibited glucose-induced insulin secretion from islets, but this effect was not specific since the structural "inactive" analogue U-73343 also inhibited insulin secretion. Likewise, in RINm5F cells, 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)P3) measured with a competitive binding assay: U-73122 failed to inhibit glucose-induced increase in Ins(1,4,5)P3. Similarly, when the effects of U-73122 and U-73343 were measured on [3H]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.
Alter
C A
CA
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Amagasu
M
M
Shah
K
K
Jolly
Y C
YC
Major
C
C
Wolf
B A
BA
D000818:Animals; D002460:Cell Line; D004963:Estrenes / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D004963:Estrenes; D007328:Insulin; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; D005985:Glyceraldehyde; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D005947:Glucose