Rescue of the Li+-induced delay of embryonic myogenesis in vitro by added inositol.
Signaling between embryonic myoblasts to coordinate gene expression is part of normal skeletal muscle development in the embryo. An unanswered question is the nature of the second messengers carrying the information to the nucleus. We have investigated the cell membrane events associated with the binding of prostaglandin to a transient receptor on the embryonic chick myoblast membrane in vitro. The membrane events include a transient change in membrane order seen by electron paramagnetic resonance (EPR), a change in cell-cell adhesion, a rapid decrease in membrane permeability and fusion of the membrane bilayers. The addition of 20 mM Li+, an inhibitor of inositol phosphate phosphatase, perturbed the transient change in membrane order and delayed the change in cell-cell adhesion and conductivity for 2-6 h. Other alkali metal ions had no such effects. The addition of inositol to the culture medium in the continued presence of Li+ restored the normal timing of the two latter events. We interpret this as evidence for an inositol phosphate second messenger system which might connect the activation of the prostaglandin receptor with the change in cell-cell adhesion, the changes in membrane conductivity and perhaps bilayer fusion. We suggest that Li+, by blocking the regeneration of polyphosphatidylinositol from inositol phosphate, reduced the efficiency of the second messenger system such that further differentiation of the myoblast membrane was delayed. The exogenous inositol provided an alternative source and membrane differentiation was unaffected.
Hausman
R E
RE
Biological Science Center, Boston University, MA 02215.
Bonincontro
A
A
Cametti
C
C
Santini
M T
MT
Indovina
P L
PL
elGendy
H
H
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004553:Electric Conductivity; D007294:Inositol / Q000494:pharmacology*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000196:embryology*
D007294:Inositol; D008094:Lithium