Mobilization of Ca2+ influx, but not of stored Ca2+, by extracellular ATP in rat submandibular gland acini.
To determine its effect on cytosolic Ca2+ levels (Ca2+i) and to assess its role as an autonomic cotransmitter, ATP was added to suspensions of rat pancreatic or submandibular gland acini loaded with fura-2. ATP had no effect on pancreatic acinar Ca2+i at either high (2.5 mM) or low (< 10 nM) extracellular Ca2+ concentrations (Ca2+o). In submandibular acini, ATP had little effect on Ca2+i when Ca2+o was < 10 nM but, with Ca2+o equal to 2.5 mM, ATP increased Ca2+i to a steady-state level 2-4 times the resting level of 50-100 nM. Addition of carbachol or epinephrine further increased Ca2+i. The mean and standard deviation of the ATP4- concentration at half of maximal activity (K0.5 ATP4-) was 33 +/- 7 microM and the Hill coefficient was 1.5 +/- 0.7 (n = 9). The active species is apparently ATP4-, as adding Mg2+ increases the total concentration of ATP needed to elevate Ca2+i. GTP, UTP, ADP and adenosine produced no significant changes in Ca2+i. However, 3'-O-(4-benzoyl)benzoyl ATP (BZATP) increased Ca2+i with a K0.5 BZATP of 2.4 +/- 0.5 microM and a Hill coefficient of 2.8 +/- 0.4 (n = 8). ATP-induced changes in Ca2+i were not due to a generalized increase in acinar-cell permeability and were unaffected by voltage-dependent Ca2+ channel blockers or by the presence of depolarizing concentrations of K+.(ABSTRACT TRUNCATED AT 250 WORDS)
Hurley
T W
TW
Departments of Child Health and Physiology, University of Missouri-Columbia, School of Medicine 65212.
Ryan
M P
MP
Shoemaker
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D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006593:Hexokinase / Q000494:pharmacology; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000166:cytology / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D002217:Carbachol; D014700:Verapamil; D006593:Hexokinase; D008274:Magnesium; D009543:Nifedipine; D000241:Adenosine; D002118:Calcium; D014544:Uridine Triphosphate; D004837:Epinephrine