Changes in indole metabolism in organ cultured rat pineal glands induced by interferon-gamma.
The purpose of this study was to test the effects of recombinant rat interferon-gamma (IFN-gamma) on rat pineal function in organ culture. The glands were pre-incubated with IFN-gamma (50, 100, and 1,000 antiviral units/ml) for two hours, followed by a stimulation with isoproterenol (ISO, 10(-6) M) (in the presence of IFN-gamma) for an additional three hours. The effect of IFN-gamma alone on the pineal function was also tested by adding another group incubated with IFN-gamma (1,000 antiviral units/ml) without ISO stimulation. The following parameters were estimated at the end of the incubation: the activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), the levels of melatonin, 5-hydroxytryptophan (5HTP), 5-hydroxytryptamine (5HT), and 5-hydroxyindole acetic acid (5HIAA), and the 5HT/5HIAA ratio. IFN-gamma had no effect on either NAT or HIOMT activities in the pineal glands. At 50 units/ml, IFN-gamma increased the melatonin content over the ISO-stimulated level in the pineal but not in the media. IFN-gamma alone, at 1,000 units/ml, also increased the melatonin content significantly over the control level. The levels of 5HTP and 5HIAA were significantly suppressed by IFN-gamma, either alone or in combination with ISO. The level of 5HT was not altered by any of the treatments. The 5HT/5HIAA ratio was significantly increased by IFN-gamma, either when given alone or when given in combination with ISO. The results suggest that IFN-gamma enhances melatonin production in the pineal gland by suppressing the oxidative deamination of 5HT to 5HIAA and shunting the biosynthetic pathway toward melatonin production.
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
B
B
Withyachumnarnkul
K O
KO
Nonaka
A M
AM
Attia
R J
RJ
Reiter
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism; D000123:Acetyltransferases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000096:biosynthesis; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012701:Serotonin / Q000378:metabolism
D007211:Indoles; D011994:Recombinant Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007371:Interferon-gamma; C030374:indole; D006916:5-Hydroxytryptophan; D000121:Acetylserotonin O-Methyltransferase; D000123:Acetyltransferases; D008550:Melatonin; D007545:Isoproterenol