Modification by Su-10'603 of the response to histamine on the production of cortisol and corticosterone in isolated canine adrenocortical cells.
The effect of Su-10'603 on the cortisol and corticosterone response to histamine in dispersed canine adrenocortical cells was examined. The production of cortisol and corticosterone in isolated dog adrenocortical cell incubations increased in a dose-dependent manner at concentrations of histamine between 0.01 and 10.0 micrograms/ml medium, with the predominant production of cortisol. When Su-10'603 (0.005 to 5.0 micrograms/ml medium), an inhibitor of 17 alpha-hydroxylation on corticosteroidogenesis, was added in cell incubations with histamine (1.0 micrograms/ml medium), the production of cortisol decreased in a reciprocal fashion, with a concomitant increase of corticosterone production. At the concentration between 0.05 and 0.1 microgram Su-10'603/ml medium, there was a shift from cortisol to corticosterone as the predominant product. These results indicate that in the dog, histamine at pathophysiological concentration stimulates steroidogenesis and acts at a relatively early stage in the biosynthetic pathway.
D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004285:Dogs; D006632:Histamine / Q000494:pharmacology*; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; C001953:SU 10603; D006632:Histamine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone