title: Pineal aryl acylamidase: effects of melatonin, serotonin-related compounds, beta-carbolines, RO4-4602 and antidepressants.
abstract: The pineal aryl acylamidase (AAA) activity has been demonstrated and characterized for the first time using ONAc as a substrate. The pineal AAA activity in the presence of 0.05% Triton X-100 was linear with protein concentration up to 1 mg and with incubation time up to 1 hour. Both the rat and bovine pineal showed a pH optimum at 5.0. The in vitro and in vivo effects of several classes of drugs on the pineal AAA activity were examined. At 0.1 mM, 5-HT, N-acetyl-5HT, melatonin, d-LSD, l-LSD, methiothepin, DA, chlorimipramine, imipramine, pargyline, TH C and harmaline significantly inhibited the rat pineal AAA activity by 19-51%. N-Acetyl-5-HT was the most potent in vitro inhibitor. However, at the same concentration, NE, 6-MeO-harman and eserine did not show any effect on the enzyme activity. Lineweaver-Burk plot indicated a competitive type of in vitro inhibition of the pineal AAA activity by melatonin. Acute subcutaneous injection of low doses (25-50 mg/kg) THBC harmaline, desipramine and protriptyline markedly inhibited the rat pineal AAA activity but at higher doses (75-100 mg/kg) the inhibition was reduced. On the contrary, RO4-4602 (200-800 mg/kg) greatly enhanced (1.5-2.3 fold) the enzyme activity, inversely proportional to the doses given. In view of the differential effects of these drugs on the brain and pineal AAA, it seems unlikely that they would be the same enzyme.
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001545:Benserazide / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010870:Pineal Gland / Q000187:drug effects / Q000201:enzymology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D002243:Carbolines; D006834:Hydrazines; D007211:Indoles; D011506:Proteins; D012701:Serotonin; D001545:Benserazide; D000581:Amidohydrolases; C019732:aryl acylamidase; D008550:Melatonin