Stimulation of colonic mucin synthesis by corticosteroids and nicotine.
1. We speculated that corticosteroids might cause beneficial stimulation of mucus synthesis, since this is a known action of carbenoxolone, itself a corticosteroid, and has also been proposed as a possible mechanism for the protective effect of smoking on ulcerative colitis. We have therefore compared the effects of corticosteroids including carbenoxolone, and nicotine on mucin synthesis, assessed by incorporation of N-[3H]acetylglucosamine into mucin by colonic epithelial biopsies in culture. 2. In histologically normal biopsies from the left colon, hydrocortisone and prednisolone caused a very marked concentration-dependent increase in mucin synthesis, with maximal effect (580 and 300% of control values respectively) at 6 mumol/l [P < 0.001, n = 35 biopsies (seven patients)] and 1.5 mumol/l [P < 0.001, n = 35 (seven patients)] respectively. The maximal effect of hydrocortisone was significantly greater than that of prednisolone (P < 0.05). Carbenoxolone, 0.17 mmol/l, also increased mucin synthesis in the left colon by 242% [P < 0.05, n = 15 (three patients)]. In contrast, these corticosteroids caused only a small, non-significant increase in mucin synthesis in the histologically normal right colon; fludrocortisone, 2 and 20 mumol/l, and aldosterone, 0.1-10 mumol/l, had no effect. Nicotine significantly increased mucin synthesis (180-220% of control values) between 62.5 nmol/l and 6.25 mumol/l (P < 0.05 at all concentrations) in both the right and left colon. In biopsies from the relatively uninvolved right colon of patients with ulcerative colitis, corticosteroids and nicotine caused relatively smaller increases in mucin synthesis. 3. The marked stimulation of mucin synthesis by corticosteroids suggests that this may account, at least in part, for their therapeutic effect in ulcerative colitis.
Finnie
I A
IA
Department of Medicine, University of Liverpool, U.K.
Campbell
B J
BJ
Taylor
B A
BA
Milton
J D
JD
Sadek
S K
SK
Yu
L G
LG
Rhodes
J M
JM
D000117:Acetylglucosamine / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D009077:Mucins / Q000096:biosynthesis*; D009538:Nicotine / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D013268:Stimulation, Chemical
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D009077:Mucins; D009538:Nicotine; D011239:Prednisolone; D002229:Carbenoxolone; D000117:Acetylglucosamine; D006854:Hydrocortisone