AJP - Cell Physiology, Vol 262, Issue 4 C934-C940, Copyright © 1992 by American Physiological Society
ATP activates a cation-permeable pathway in rat parotid acinar cells
S. P. Soltoff, M. K. McMillian and B. R. Talamo
Department of Physiology, Tufts University, Boston, Massachusetts 02111.
Effects of several purinergic receptor agonists were examined on rat
parotid acinar cells. Extracellular ATP stimulated 45Ca2+ uptake into
isolated rat parotid acinar cells in a concentration-dependent fashion
(EC50 approximately 125 microM ATP) at a maximum rate of approximately 6
nmol.mg protein-1.min-1. In the absence of extracellular Na+, ATP increased
the uptake rate by greater than 100%. Increasing concentrations of
extracellular Na+ reduced the ATP-stimulated rate of 45Ca2+ entry in a
graded fashion (IC50 16.6 mM), suggesting that Ca2+ and Na+ compete for
entry. Uptake rate was not reduced when intracellular Ca2+ was buffered
with 1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid, indicating
that the effects of ATP were not initiated by an elevation in intracellular
free Ca2+ concentration. 3-O-(4'-benzoyl)benzoyl-ATP was much more potent
(EC50 approximately 4 microM) and stimulated Ca2+ influx at a greater rate
(approximately 12 nmol.mg protein-1.min-1) than ATP. Other nucleotide
analogues, including adenosine 5'-O-(3-thiotriphosphate), 2-methylthio-ATP,
and 5'-adenylylimidodiphosphate, were much less effective than ATP. ATP
produced a biphasic effect on membrane potential: an initial
hyperpolarization was followed by a rapid depolarization. The
depolarization was greatly reduced in the absence of extracellular Na+, but
not in the absence of extracellular Ca2+, indicating that the majority of
the depolarizing current was due to Na+ entry. Effects of ATP on the
membrane potential were distinguishable from those of the Ca2+ ionophore
ionomycin and the muscarinic agonist carbachol. Depolarization of the cells
by gramicidin or K+ did not produce an increase in 45Ca2+ uptake.(ABSTRACT
TRUNCATED AT 250 WORDS)
