ATP activates a cation-permeable pathway in rat parotid acinar cells.
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)
Soltoff
S P
SP
Department of Physiology, Tufts University, Boston, Massachusetts 02111.
McMillian
M K
MK
Talamo
B R
BR
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002412:Cations / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004594:Electrophysiology; D007477:Ions; D008564:Membrane Potentials; D010306:Parotid Gland / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011687:Purines / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000493:pharmacokinetics
D002412:Cations; D007477:Ions; D011687:Purines; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium