Selectivity in inositol phosphate production following pancreatic acinar cell desensitization

The effects of pancreatic acinar cell desensitization by carbamylcholine (Cch), caerulein (Cae) and the phorbol ester TPA on the production of inositol tris and tetrakisphosphates were studied. In control acini, Cch and Cae caused comparable increases in Ins (1,4,5) P3, Ins (1,3,4,5) P4 and Ins (1,3,4) P3 after 15 sec stimulation. Desensitization by Cch totally inhibited the subsequent production of all three inositol phosphates in response to Cch. Desensitization by Cae allowed a subsequent production of all three inositol phosphates in response to Cae, but with a significant reduction. Desensitization by TPA reduced the production of Ins (1,4,5) P3 in response to Cch and Cae and totally inhibited that of the two other inositides. These data point to phospholipase C as a prime target for the altered production of inositol phosphates.