Abstract
The nocturnal increase in circulating melatonin in vertebrates is regulated by 10- to 100-fold increases in pineal serotonin N-acetyltransferase (AA-NAT) activity. Changes in the amount of AA-NAT protein were shown to parallel changes in AA-NAT activity. When neural stimulation was switched off by either light exposure or L-propranolol-induced beta-adrenergic blockade, both AA-NAT activity and protein decreased rapidly. Effects of L-propranolol were blocked in vitro by dibutyryl adenosine 3',5'-monophosphate (cAMP) or inhibitors of proteasomal proteolysis. This result indicates that adrenergic-cAMP regulation of AA-NAT is mediated by rapid reversible control of selective proteasomal proteolysis. Similar proteasome-based mechanisms may function widely as selective molecular switches in vertebrate neural systems.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adrenergic beta-Agonists / pharmacology
-
Adrenergic beta-Antagonists / pharmacology
-
Animals
-
Arylamine N-Acetyltransferase / metabolism*
-
Bucladesine / pharmacology
-
Cyclic AMP / metabolism
-
Cysteine Endopeptidases / metabolism*
-
Cysteine Proteinase Inhibitors / pharmacology
-
Isoproterenol / pharmacology
-
Light
-
Melatonin / biosynthesis*
-
Multienzyme Complexes / metabolism*
-
Pineal Gland / cytology
-
Pineal Gland / drug effects
-
Pineal Gland / enzymology
-
Pineal Gland / metabolism*
-
Propranolol / pharmacology
-
Proteasome Endopeptidase Complex
-
Rats
-
Receptors, Adrenergic, beta / physiology
Substances
-
Adrenergic beta-Agonists
-
Adrenergic beta-Antagonists
-
Cysteine Proteinase Inhibitors
-
Multienzyme Complexes
-
Receptors, Adrenergic, beta
-
Bucladesine
-
Propranolol
-
Cyclic AMP
-
Arylamine N-Acetyltransferase
-
Cysteine Endopeptidases
-
Proteasome Endopeptidase Complex
-
Melatonin
-
Isoproterenol