The effects of nicotine, cotinine and anabasine on rat adrenal 11β-hydroxylase and 21-hydroxylase

The effects of nicotine, cotinine and anabasine on rat adrenal steroidogenesis were examined by spectral and enzymatic techniques. The addition of nicotine, cotinine or anabasine to preparations of rat adrenal mitochondria produced type II cytochrome P-450 difference spectra. The addition of nicotine or anabasine, but not cotinine, to rat adrenal microsomes yielded type II cytochrome P-450 difference spectra. Nicotine and anabasine competitively inhibited rat adrenal mitochondrial 11β-hydroxylase and microsomal 21-hydroxylase. Cotinine competitively inhibited mitochondrial 11β-hydroxylase, but did not inhibit microsomal 21-hydroxylase. The apparent enzymatic inhibition constants for cotinine, nicotine, anabasine and metyrapone inhibition of the mitochondrial 11β-hydroxylase were 32, 96, 120 and 74 μM respectively. These studies suggest that components of cigarette smoke may alter patterns of adrenal steroidogenesis.