Effects of lead ions on events associated with exocytosis in isolated bovine adrenal medullary cells.
Lead buffers (citrate and Tiron) were used to investigate the effects of low concentrations (0.1-6 microM) of Pb2+ on stimulus-secretion coupling in isolated bovine chromaffin cells. Nicotinic agonists and high K elicit secretion by enhancing Ca2+ influx into chromaffin cells. Pb2+ inhibited the catecholamine secretion in response to 500 microM carbachol and 77 mM K+ depolarization but was without significant effect on basal secretion. Pb2+ also inhibited the influx of 45Ca occurring in response to these agents. The K0.5 values for inhibition suggest that the carbachol-evoked flux is more sensitive to Pb2+ than influx in response to a direct depolarization. When extracellular calcium was lowered in the absence of Pb2+, both secretion and 45Ca entry were reduced. The effects of Pb2+ were comparable to those of lowered Ca2+. 22Na influx through nicotinic receptor-mediated channels, measured in the presence of tetrodotoxin (2 microM) and ouabain (50 microM), was inhibited by Pb2+. The results suggest that Pb2+ inhibits exocytotic catecholamine secretion by inhibiting Ca2+ influx. The differential sensitivity to Pb2+ of K- and carbachol-evoked 45Ca flux, coupled with the 22Na measurements, indicates that Pb2+ inhibits the movement of ions through acetylcholine-induced channels as well as through voltage-sensitive calcium channels.
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D002469:Cell Separation; D005071:Evoked Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects*; D007854:Lead / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D007854:Lead; D013779:Tetrodotoxin; D010042:Ouabain; D002217:Carbachol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium