title: A study of the cellular mechanism by which lead affects catecholamine secretion.
abstract: 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.
authors.affiliation: University of Texas Southwestern Medical Center, Department of Obstetrics & Gynecology, Dallas 75235-9032, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Ramin
authors.forename: J C
authors.initials: JC
authors.lastname: Porter
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002395:Catecholamines / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology*; D008954:Models, Biological; D009281:Naphthalenes / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology; D010673:Pheochromocytoma; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002147:Calmodulin; D002395:Catecholamines; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009566:Nitrates; D013449:Sulfonamides; D013873:Thionucleotides; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D007854:Lead; C017967:W 7; C017461:lead nitrate; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; C058819:calphostin C