AJP - Cell Physiology, Vol 248, Issue 3 203-C216, Copyright © 1985 by American Physiological Society
Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver
J. R. Williamson, R. H. Cooper, S. K. Joseph and A. P. Thomas
Receptor occupation by a variety of Ca2+-mobilizing hormones, such as alpha
1-adrenergic agents, vasopressin and angiotensin II, causes a rapid
phosphodiesterase-mediated hydrolysis of
phosphatidylinositol-4,5-bisphosphate in the plasma membrane with the
production of the water soluble compound myo-inositol-1,4,5-trisphosphate
(IP3) and the lipophilic molecule 1,2-diacylglycerol (DG). This review
summarizes the recent evidence obtained in the liver that defines the roles
of these products as intracellular messengers of hormone action.
Intracellular Ca2+ mobilization is mediated by IP3, which releases Ca2+
from a subpopulation of the endoplasmic reticulum, resulting in a rapid
increase of the cytosolic free Ca2+ concentration ( [Ca2+]i). Further
effects of receptor occupancy are inhibition of the plasma membrane
Ca2+-ATPase, despite net Ca2+ efflux, and an increased permeability of the
plasma membrane to extracellular Ca2+. The activation of the
phospholipid-dependent protein kinase C by DG does not alter Ca2+ fluxes
across the plasma membrane. In contrast to some secretory cells, a
synergism between protein kinase C activation and increased [Ca2+]i is not
observed in liver. Activation of protein kinase C profoundly inhibits the
response to alpha 1-adrenergic agonists, with only minimal effects on the
vasopressin response. It is concluded that in liver the two inositol-lipid
messenger systems, IP3 and DG, exert their effects by essentially separate
pathways.
