AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 6 1043-G1050, Copyright © 1995 by American Physiological Society
Phosphoinositide synthesis in desensitized rat pancreatic acinar cells
J. S. Lods, B. Rossignol, C. Dreux and J. Morisset
Departement de Biologie, Faculte des Sciences, Universite de Sherbrooke, Quebec, Canada.
To help understand the possible role of phosphoinositide turnover in the
desensitization process, the availability of phosphatidylinositol
4,5-bisphosphate was investigated in normal and desensitized pancreatic
acinar cells treated with carbamylcholine (Cch), caerulein (Cae), and the
phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In control acini,
incorporation of [myo-3H]inositol into total phosphoinositides was maximal
at 120 min, was Cch and Cae dose dependent, and was insensitive to TPA. Cch
stimulation increased the proportion of [myo-3H]inositol incorporated into
phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], whereas Cae
specifically channeled [myo-3H]inositol incorporation into
phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol
3,4,5-trisphosphate. In the desensitized cells, preexposure to Cch and Cae,
but not to TPA, increased the subsequent basal rate of [myo-3H]inositol
incorporation into total phosphoinositol (PI) by 66 and 50% above control
values. There were no subsequent responses to increasing concentrations of
Cch, Cae, and TPA during a second incubation. Desensitization of the
pancreatic secretory responses to Cch, Cae, and TPA does not seem to result
from a decrease either in total PI or in specific PtdIns(4,5)P2 synthesis,
which is needed for inositol trisphosphate and diacylglycerol production.
