Nitric oxide donors induce calcium-mobilisation from internal stores but do not stimulate catecholamine secretion by bovine chromaffin cells in resting conditions.
The potential role of nitric oxide (NO) donors and peroxynitrites on both basal catecholamine (CA) secretion and modulation of calcium levels has been investigated in primary cultures of bovine chromaffin cells. NO donors did not modulate catecholamine secretion, while peroxynitrites induced a time dose-dependent increase in basal CA secretion. Two facts may explain the lack of these compounds on basal CA secretion. NO donors induce, on the one hand, an increase in intracellular calcium levels by depletion of internal IP3-stores from endoplasmic reticulum. On the other hand, a small calcium influx through N-type voltage-dependent calcium channels (VDCC), which seem not to be coupled to exocytosis of adrenaline and noradrenaline in chromaffin cells. Both effects, calcium-mobilisation from internal stores and calcium entry through N-type VDCC are mediated by cGMP synthesis. In contrast, peroxynitrites induce an increase in basal CA secretion by both a decrease of intracellular catecholamine content and a toxic effect on cellular membrane. All these results, taken together, could explain contradictory results in the literature on the role of NO on basal catecholamine secretion and on modulation of intracellular calcium in chromaffin cells.
Vicente
S
S
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, E-28040 Madrid, Spain.
Figueroa
S
S
Pérez-Rodríguez
R
R
González
M P
MP
Oset-Gasque
M J
MJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D002395:Catecholamines; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006152:Cyclic GMP; D002118:Calcium