Status of dopamine in bovine pineal glands and the stimulation of N-acetyltransferase activity by D2-dopaminergic receptor agonists in the rat pineal glands in culture.
In a previous study, we identified in the bovine pineal gland two [3H]spiroperidol-binding sites with KD values of 0.18 and 2.1 nM and Bmax values of 37 and 630 fmol/mg protein, respectively. In this study, the status of dopamine in the bovine pineal glands was delineated further by measuring the relative concentrations of dopamine and norepinephrine and the relative concentrations of serotonin and melatonin. Furthermore, the presence of 4.0 +/- 0.6 micrograms/dopamine/gm tissue encouraged us to delineate the effects of select dopaminergic receptor agonists and antagonists on the synthesis of melatonin in vivo and on the activity of N-acetyltransferase in the rat pineal gland in culture. The acute administration of haloperidol (3 mg/kg intraperitoneally [ip]) or sulpiride (200 mg/kg ip) increased the concentration of melatonin in the pineal gland from 160.6 +/- 8.18 to 327.6 +/- 45.43 and 306.5 +/- 40.53 pg/gland, respectively. Dopamine exhibited dual effects on the activity of N-acetyltransferase, inhibiting the basal activity at 0.1 microM and stimulating it at 10 microM, and the later effect was blocked by propranolol. D2-dopaminergic receptor agonists such as bromocriptine (4.0 microM) or LY-171555 (10.0 microM) partially attenuated the norepinephrine-induced stimulation of N-acetyltransferase, and these attenuating effects were reversed by D2-dopaminergic antagonists such as haloperidol (10 microM) or domperidone (10 microM). The results of these studies are interpreted to indicate that for the synthesis of melatonin, the pineal D2-dopaminergic receptors may function independently from those of the beta 1-adrenergic receptor sites. Furthermore, the said D2-dopaminergic receptor are amenable to down regulation since the activity of N-acetyltransferase remained unaltered (0.0717 vs. 0.0729 nmol/gland/h) following chronic treatment (4 mg/kg ip/day for 30 days) with bromocriptine.
Govitrapong
P
P
Department of Pharmacology, University of Nebraska College of Medicine, Omaha 68105.
Hama
Y
Y
Pfeiffer
R
R
Ebadi
M
M
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004298:Dopamine / Q000032:analysis*; D015259:Dopamine Agents / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008550:Melatonin / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000032:analysis* / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology
D015259:Dopamine Agents; D012701:Serotonin; D013469:Sulpiride; D000123:Acetyltransferases; D006220:Haloperidol; D008550:Melatonin; D004298:Dopamine; D009638:Norepinephrine