Extracellular atp modulates [ca2+]i in retinoic acid-treated
embryonic chondrocytes.
Hung, Clark T., Fred D. Allen, Kyle D. Mansfield, and Irving M.
Shapiro.
Center for Biomedical Engineering, Columbia University, New York,
NY 10032, Dept. of Bioengineering, School of Engineering and Applied
Sciences, Univ. of Pennsylvania, Philadelphia, PA 19104-6392, Dept.
of Biochemistry, School of Dental Medicine, Univ. of Pennsylvania,
Philadelphia, PA 19104-6003
APStracts 3:0399C, 1996.
Treated with low doses of retinoic acid (RA), cephalic chondrocytes of
the chick embryonic sternum mature and express phenotypic
characteristics of post-mitotic hypertrophic cells. In concert with
these maturation-dependent changes, cells release adenine nucleotides
into the culture medium. To ascertain if these compounds modulate
chondrocyte function, we challenged chondrocytes with nucleotides and
measured one determinant of the signal transduction pathway, [Ca2+]i.
In the presence of micromolar concentrations of ATP, there was a dose
dependent elevation in chondrocyte [Ca2+]i; ADP caused a small but
significant rise in the peak [Ca2+]i response. We found that the
change in the [Ca2+]i response is linked to retinoid-dependent
maturation of chondrocytes. Thus, the [Ca2+]i rise was dependent on
the RA concentration and treatment time. Immature caudal
chondrocytes, cells that were not affected by RA, were used as
control cells for this study. When treated with ATP, these cells did
not exhibit a [Ca2+]i response. Although the purinergic subtype
receptor was not characterized, the observation that cells responded
to ATP and ADP, but were refractory to AMP and adenosine suggested
that P2 receptors were expressed by chondrocytes. Since during the
same culture period, chondrocytes exhibited many of the unique
characteristics of the terminally differentiated cell, the
acquisition of purinergic receptors represents a new feature
associated with expression of the mature phenotype. Finally, to
ascertain if the ATP-dependent response was due to release of Ca2+
from intracellular stores, cells were treated with thapsigargin. As
this compound significantly reduced the [Ca2+]i signal, we concluded
that the ATP response is mediated by release of cations from the
endoplasmic reticulum.
Received 31 July 1996; accepted in final form 4 December 1996.
APS Manuscript Number C428-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996