Somatostatin inhibition of phospholipase C activity in isolated rat pancreatic islets.
We have assessed the effect of somatostatin on the phospholipase C activity in isolated rat pancreatic islets. The phospholipase C activity was measured as the generation of inositol 1,4,5-trisphosphate and its metabolite inositol 1,3,4-trisphosphate from the hydrolysis of polyphosphoinositides. Inositol phosphates were measured using anion-exchange fast protein liquid chromatography analysis of extracts from islets prelabelled with myo-[3H]inositol. Somatostatin (1-1000 nmol l-1) significantly inhibited the glucose-induced (12 mmol l-1) phospholipase C activity in a concentration-dependent manner. The Ca2+ channel blocker verapamil (25 mumol l-1) also inhibited the glucose-induced (12 mmol l-1) phospholipase C, whereas the combination of somatostatin and verapamil did not induce any additional inhibition. At 3.3 mmol l-1 glucose, the hypoglycaemic sulphonylurea, tolbutamide (1 mmol l-1), increased the phospholipase C activity. This effect was reversed by somatostatin (100 nmol l-1). Tolbutamide did not further increase the glucose-induced (12 mmol l-1) phospholipase C activity. However, the somatostatin inhibition of glucose-induced (12 mmol l-1) phospholipase C was reversed by tolbutamide. The activator of adenylyl cyclase, forskolin (20 mumol l-1), did not exert any effect on the PLC-inhibition of somatostatin, whereas forskolin alone inhibited the phospholipase C activation at 12 mmol l-1 glucose. Our study demonstrates that somatostatin inhibits the hydrolysis of polyphosphoinositides in pancreatic islets, apparently via a mechanism dependent on Ca2+ and not on cAMP.
Malm
D
D
Institute of Clinical Medicine, University of Tromsø, Norway.
Giaever
A
A
Vonen
B
B
Burhol
P G
PG
Florholmen
J
J
D000818:Animals; D002118:Calcium / Q000502:physiology; D002853:Chromatography, Liquid; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*; D014700:Verapamil / Q000494:pharmacology
D007295:Inositol Phosphates; D005576:Colforsin; D013004:Somatostatin; D014044:Tolbutamide; D014700:Verapamil; D000242:Cyclic AMP; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium