Evidence that interferon-gamma alters pineal metabolism both indirectly via sympathetic nerves and directly on the pinealocytes.
1. Interferon-gamma (IFN-gamma) has been shown to suppress N-acetyltransferase (NAT) activity in cultured rat pineal glands when stimulated with isoproterenol (ISO). 2. Conversely, IFN-gamma has also been shown to increase the melatonin content of the rat pineal gland in organ culture. 3. Circumstantial evidence leads to a hypothesis that the NAT suppressive effect may be due to the action of IFN-gamma on the sympathetic nerve terminals. 4. To test this hypothesis, pineal glands from intact (INT) and superior cervical ganglionectomized (SCGX) rats, which had been operated 5 days earlier, were cultured with either ISO or ISO + IFN-gamma. 5. The concentration of ISO was 10(-8) M and that of IFN-gamma was 300 antiviral units/ml. 6. The pineals were incubated for a total period of 5.5 hr, after which the activities of NAT and hydroxyindole-O-methyltransferase (HIOMT) and the levels of melatonin and cAMP were estimated. 7. Suppression of NAT by IFN-gamma was observed in the pineals from INT rats, but not in those from SCGX animals. 8. IFN-gamma significantly enhanced melatonin levels over those in ISO-stimulated pineals and culture media from the SCGX animals, but not from the INT animals. 9. IFN-gamma treatment had no effect on either the HIOMT activity or cAMP levels. 10. The results indicate that the IFN-gamma-induced NAT suppression requires the integrity of the sympathetic nerve terminals and the IFN-gamma-induced enhancement of melatonin production is accomplished through its direct action on pinealocytes.
Withyachumnarnkul
B
B
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Reiter
R J
RJ
Lerchl
A
A
Nonaka
K O
KO
Stokkan
K A
KA
D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000378:metabolism*
D007371:Interferon-gamma; D000242:Cyclic AMP; D000121:Acetylserotonin O-Methyltransferase; D001191:Arylamine N-Acetyltransferase