TY - JOUR
T1 - A study of the cellular mechanism by which lead affects catecholamine secretion
AU - Ramin, Susan M.
AU - Porter, John C.
N1 - Funding Information:
This research was supported by the American Association of Obstetricians and Gynecologists Foundation.
PY - 1997/8/22
Y1 - 1997/8/22
N2 - Our purpose was to determine the role of protein kinases in the mediation of the stimulatory effects of lead on catecholamine secretion. Pheochromocytoma cells were incubated for 90 minutes with W-7 (calmodulin antagonist), calphostin C (protein kinase C inhibitor), Sp-cAMPS (cAMP agonist), Rp-cAMPS (cAMP antagonist), forskolin (activator of adenylyl cyclase), or lead nitrate. Catecholamines were measured by liquid chromatography. Lead had a stimulatory effect on catecholamine secretion, whereas W-7 was inhibitory. In the presence of both lead and W-7, the response was markedly decreased compared to that seen with lead alone. Calphostin C suppressed the secretion of catecholamines; however, in the presence of lead and calphostin C, the secretion was similar to that seen with lead alone. Compared to control, Sp-cAMPS was stimulatory. Co-incubation of Sp-cAMPS and lead had a slight synergistic effect. Rp-cAMPS decreased catecholamine secretion, but co-incubation of Rp-cAMPS and lead resulted in a slight reduction compared to lead alone. Forskolin markedly increased the secretion of catecholamines, and co-incubation of lead and forskolin resulted in a synergistic increase. In the absence of calcium, lead had no effect. We conclude that lead stimulates catecholamine secretion by acting through the calcium/calmodulin-dependent protein kinase II system and not through the protein kinase C or protein kinase A system, and requires the presence of calcium for its action.
AB - Our purpose was to determine the role of protein kinases in the mediation of the stimulatory effects of lead on catecholamine secretion. Pheochromocytoma cells were incubated for 90 minutes with W-7 (calmodulin antagonist), calphostin C (protein kinase C inhibitor), Sp-cAMPS (cAMP agonist), Rp-cAMPS (cAMP antagonist), forskolin (activator of adenylyl cyclase), or lead nitrate. Catecholamines were measured by liquid chromatography. Lead had a stimulatory effect on catecholamine secretion, whereas W-7 was inhibitory. In the presence of both lead and W-7, the response was markedly decreased compared to that seen with lead alone. Calphostin C suppressed the secretion of catecholamines; however, in the presence of lead and calphostin C, the secretion was similar to that seen with lead alone. Compared to control, Sp-cAMPS was stimulatory. Co-incubation of Sp-cAMPS and lead had a slight synergistic effect. Rp-cAMPS decreased catecholamine secretion, but co-incubation of Rp-cAMPS and lead resulted in a slight reduction compared to lead alone. Forskolin markedly increased the secretion of catecholamines, and co-incubation of lead and forskolin resulted in a synergistic increase. In the absence of calcium, lead had no effect. We conclude that lead stimulates catecholamine secretion by acting through the calcium/calmodulin-dependent protein kinase II system and not through the protein kinase C or protein kinase A system, and requires the presence of calcium for its action.
KW - Catecholamine secretion
KW - Lead
KW - Pheochromocytoma cells
KW - Protein kinases
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U2 - 10.1016/S0024-3205(97)00676-0
DO - 10.1016/S0024-3205(97)00676-0
M3 - Article
C2 - 9324073
AN - SCOPUS:0030847712
VL - 61
SP - 1313
EP - 1321
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 13
ER -