Lanthanum: inhibition of ACTH-stimulated cyclic AMP and corticosterone synthesis in isolated rat adrenocortical cells.
Lanthanum (La+++) is a well-known Ca++ antagonist in a number of biological systems. It was used in the present study to examine the role of Ca++ in the regulation of adenyl cyclase of the adrenal cortex by ACTH. In micromolar concentrations, .La+++ inhibited both cyclic AMP and corticosterone response of isolated adrenal cortex cells to ACTH. However, a number of intracellular processes were not affected by La+++. These include the stimulation of steroidogenesis by dibutyryl cyclic AMP, conversion of several steroid precursors into corticosterone, and stimulation of the latter by glucose. Thus, inhibition of steroidogenesis by La+++ appears to be solely due to an inhibition of ACTH-stimulated cyclic AMP formation. Electron microscope examination showed that La+++ was localized on plasma membrane of the cells and did not appear to penetrate beyond this region. Since La+++ is believed to replace Ca++ at superficial binding sites on the cell membrane, it is proposed that Ca++ at these sites plays an important role in the regulation of adenyl cyclase by ACTH. Similarities in the role of Ca++ in "excitation-contraction" coupling and in the ACTH-adenyl cyclase system raise the possibility that a contractile protein may be involved in the regulation of adenyl cyclase by those hormones which are known to require Ca++ in the process.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000096:biosynthesis*; D003900:Desoxycorticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006908:Hydroxyprogesterones / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology*; D008854:Microscopy, Electron; D008954:Models, Biological; D011284:Pregnenolone / Q000378:metabolism; D051381:Rats
D006908:Hydroxyprogesterones; D003900:Desoxycorticosterone; D003994:Bucladesine; D007811:Lanthanum; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D002118:Calcium; D003345:Corticosterone