RT Journal Article
SR Electronic
T1 Pineal Gland in Organ Culture
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 164
OP 171
VO 6
IS 2
A1 DAVID C. KLEIN
A1 JACK ROWE
YR 1970
UL http://molpharm.aspetjournals.org/content/6/2/164.abstract
AB The effect of harmine on serotonin-14C metabolism by pineal glands in organ culture was studied to examine the possibility that inhibition of monoamine oxidase activity would result in stimulation of melatonin-14C formation. Glands treated with harmine (0.1-10 µM) produced 2-5 times more radiolabeled melatonin than did untreated controls. Thin layer chromatographic analysis of culture media revealed that harmine treatment increased N-acetylserotonin-14C as well as melatonin-14C levels, and decreased the production of hydroxyindoleacetic acid-14C, hydroxytryptophol-14C, and methoxytryptophol-14C. The activity of hydroxyindole O-methyltransferase in harmine-treated glands, or in homogenates of untreated glands to which harmine had been added, was no different from that of untreated controls. These observations suggest that inhibition of oxidation of serotonin resulted in enhanced N-acetylation and that the resulting high levels of N-acetylserotonin caused increased melatonin production by a mechanism not dependent upon increased production of hydroxyindole O-methyltransferase. This effect can be explained on the basis of mass action. ACKNOWLEDGMENTS The authors wish to acknowledge the expert technical assistance of Miss Orisha Kowarko and Mrs. Amy Doty. They are also indebted to Dr. Lawrence Raisz, in whose laboratories this work was performed. The critical suggestions of Dr. Raisz and Dr. Angelo Notides during the preparation of this manuscript are greatly appreciated.