Activation of P2z purinoceptors diminishes the muscarinic cholinergic-induced release of inositol 1,4,5-trisphosphate and stored calcium in rat parotid acini. ATP as a co-transmitter in the stimulus-secretion coupling.
The effect of extracellular ATP on the intracellular free Ca2+ concentration ([Ca2+]i) and inositol phosphate production following stimulation with the muscarinic cholinergic agonist acetylcholine (ACh) was investigated in isolated rat parotid acinar cells. Stimulation of rat parotid acinar cells with ATP4- results in a rise in [Ca2+]i that is due to influx of extracellular Ca2+ and mobilization of Ca2+ from intracellular stores. Stimulation with purinergic agonists revealed that both influx as well as Ca2+ release from intracellular stores was mediated through activation of P2z receptors. The Ca2+ mobilization from intracellular stores was due to production of Ins(1,4,5)P3 and was inhibited by U73122, an inhibitor of phospholipase C-coupled processes. Under Ca(2+)-free conditions ATP4- caused a dose-dependent inhibition (IC50 = 8 microM) of the ACh-evoked Ca2+ release. The inhibitory effect of ATP4- is due to activation of the P2z purinoceptors, which results in a strong reduction in the ACh-induced inositol phosphate production. Prestimulation with 100 microM ATP4- reduced the amount of Ins(1,4,5)P3 formed after maximal ACh stimulation by 91%. In conclusion, the inhibitory effect of ATP4- on the ACh-mediated response is due to interactions of the activated P2z receptor with the phospholipase C-coupled processes underlying the muscarinic cholinergic response.
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
T D
TD
Jørgensen
J
J
Gromada
K
K
Tritsaris
B
B
Nauntofte
S
S
Dissing
D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018678:Cholinergic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010306:Parotid Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D018678:Cholinergic Agents; D007295:Inositol Phosphates; D018048:Receptors, Purinergic P2; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D002118:Calcium