The role of calcium in the mechanism of corticotropin releasing factor mediated ACTH release.
To investigate the role of calcium (Ca+2) in CRF stimulated ACTH release, we studied the effect of the following conditions on CRF (10 nM) mediated ACTH release in primary pituitary monolayer culture: different concentrations of Ca+2; EGTA; lanthanum (La+3) and nifedipine, blockers of calcium cell influx and penfluridol, trifluoperazine, and pimozide, inhibitors of calmodulin activation. Higher concentrations of Ca+2 in the culture medium led to greater amounts of CRF induced ACTH release. EGTA at 3 mM decreased the amount of CRF stimulated ACTH release by 60% but did not alter the spontaneous release of ACTH. At 0.5 mM and 1.0 mM La+3, ACTH release induced by CRF was inhibited by 23% and 35% respectively (p less than 0.01). Nifedipine (both 10(-5) and 10(-4) M) inhibited CRF stimulated ACTH release but only to a maximum of 30%. This inhibition was completely overcome by the addition of 12 mM calcium. Penfluridol, pimozide, and trifluoperazine blocked the release of ACTH induced by CRF by 63%, 26%, and 0% respectively. In conclusion, extracellular Ca+2, Ca+2 influx, and calmodulin play a role in the mechanism of CRF stimulated ACTH in vitro.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003470:Culture Media; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D009543:Nifedipine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D002121:Calcium Channel Blockers; D003470:Culture Media; D004533:Egtazic Acid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D009543:Nifedipine; D002118:Calcium