Effect of clonidine on the activity of tryptophan hydroxylase from rat brainstem following in vivo or in vitro treatment.
In vivo administration of clonidine hydrochloride (Catapres) via tail vein injection produced a rapid increase in brainstem tryptophan hydroxylase activity assayed in vitro under subsaturating conditions of reduced pterin cofactor, 6MPH4. Enzyme activity returned to and remained at control levels about 60 min after treatment with low doses of clonidine (5 micrograms/kg). However, with higher doses of the drug (15 micrograms/kg), enzyme activity fell to below control levels for about an hour. Incubation of brainstem slices with clonidine also produced a dose-dependent increase in enzyme activity. The increase in enzyme activity appears to be mediated indirectly since it was abolished when brain catecholamine levels were depleted by pretreatment with 6-hydroxydopamine 8 days prior to clonidine treatment. The kinetic properties of tryptophan hydroxylase prepared 25 and 90 min after clonidine administration indicate that the initial increase and subsequent decrease in enzyme activity seen under these conditions may be due to changes in apparent Vmax of the enzyme.
Weekley
L B
LB
Phan
T
T
Narasimhachari
N
N
Johannessen
J
J
Boadle-Biber
M C
MC
D000818:Animals; D001933:Brain Stem / Q000201:enzymology*; D002540:Cerebral Cortex / Q000032:analysis; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D014365:Tryptophan Hydroxylase / Q000032:analysis*
D006892:Hydroxydopamines; D011985:Receptors, Serotonin; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D014365:Tryptophan Hydroxylase; D003000:Clonidine