Calmodulin inhibitors decrease the CRF-and AVP-induced ACTH release in vitro: interaction of calcium-calmodulin and the cyclic AMP system.
The effect of N-(6-aminohexyl)-5-chloro-naphthalene-1-sulfomide (W-7) and trifluoperazine (TFP) was examined on ACTH release from cultured rat anterior pituitary cells and pituitary halves. These drugs significantly inhibited the ACTH release induced by synthetic ovine corticotropin-releasing factor (CRF) in a dose-related manner. In pituitary halves, arginine vasopressin (AVP) at 10 and 100 ng/ml showed almost the same ACTH-releasing activity as CRF at the same concentrations. W-7 and TFP inhibited the CRF-and AVP-induced ACTH release from pituitary halves. The cyclic AMP levels in the pituitary halves were significantly increased by CRF, but not AVP. Although W-7 inhibited CRF-induced ACTH release, it did not have an effect in cyclic AMP accumulation. These results suggest that CRF exerts ACTH-releasing activity through both the calcium-calmodulin system and cyclic AMP system and that AVP stimulates ACTH release mainly through the calcium-calmodulin system.
Murakami
K
K
Hashimoto
K
K
Ota
Z
Z
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000502:physiology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; D001127:Arginine Vasopressin; D014268:Trifluoperazine; C017967:W 7; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D002118:Calcium