PT  - JOURNAL ARTICLE
AU  - SUSAN P. C. COLE
AU  - RALPH ALLEN WHITNEY
AU  - GERALD S. MARKS
TI  - Ferrochelatase-Inhibitory and Porphyrin-Inducing Properties of 3,5-Diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine and Its Analogues in Chick Embryo Liver Cells
DP  - 1981 Sep 01
TA  - Molecular Pharmacology
PG  - 395--403
VI  - 20
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/20/2/395.short
4100  - http://molpharm.aspetjournals.org/content/20/2/395.full
SO  - Mol Pharmacol1981 Sep 01; 20
AB  - A series of analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) was investigated for ferrochelatase-inhibitory and porphyrin-inducing activities in chick embryo liver cell cultures. It was found that, in order to inhibit ferrochelatase maximally, a DDC analogue must be a dihydropyridine with ester groups in positions 3 and 5, and an alkyl substituent in position 4. The structural requirements for porphyrin-inducing activity were less stringent. The pattern of porphyrin accumulation produced in response to DDC and its analogues was investigated using high-performance liquid chromatography. Protoporphyrin was found to be the major porphyrin to accumulate in response to dihydropyridine analogues that inhibited ferrochelatase. Uro- and heptacarboxylic porphyrins were the major porphyrins to accumulate in response to all of the pyridine analogues. A pattern of porphyrin accumulation very similar to that produced by the pyridine analogues was observed with those dihydropyridine analogues which did not inhibit ferrochelatase, suggesting that these dihydropyridines are readily converted to pyridines in the chick embryo liver cell culture. It is clear that some analogues of DDC induce porphyrin accumulation by a mechanism other than through ferrochelatase inhibition. ACKNOWLEDGMENTS The authors wish to thank Mr. Scott Follows, Ms. Frances Taylor, and Ms. Anne Weary for their able technical assistance. We are grateful to Ms. Debbie Browne for her help in the preparation of the manuscript.