Effects of adrenergic drugs on the activity of tryptophan hydroxylase in midbrain raphe slices of the rat.
The effects of ?- and ss-adrenergic drugs on the activity of tryptophan hydroxylase were investigated in rat midbrain raphe slices. The tryptophan hydroxylase activity in slices was estimated by measuring the formation of 5-hydroxytryptophan (5-HTP) under inhibition of aromatic l-amino acid decarboxylase using 3-hydroxy-4-bromobenzyloxyamine (NSD 1055). Isoproterenol, a ss-adrenergic stimulant, significantly increased 5-HTP formation to 122% (P < 0.05) of control at 10(?6) M and this effect was prevented by 10(?6) M of propranolol, a ss-adrenergic blocker. 5-(1-Hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostryril hydrochloride hemihydrate (OPC 2009), a ss-adrenergic stimulant which does not contain a catechol group, increased 5-HTP formation to 145% at 10(?6) M. A-23187 at 5 x 10(?7) M further enhanced the isoproterenol-stimulated 5-HTP formation to 156% of control. Dibutyryl cAMP at 10(?2) M, however, did not enhance it. 8-Bromo cAMP did not enhance the OPC 2009-stimulated 5-HTP formation, either. An ?-adrenergic stimulant, clonidine, had no effect on 5-HTP formation. But an ?-adrenergic blocker, yohimbine, reduced 5-HTP formation to 78% at 10(?6) M. These results suggest that the activity of tryptophan hydroxylase can be controlled by a ss-adrenergic receptor coupled with adenylate cyclase via an intracellular cAMP-dependent process.
Sawada
M
M
Laboratory of Cell Physiology, Department of Life Chemistry, Graduate School at Nagatsuta, Tokyo Institute of Technology, Yokohama 227, Japan.
Nagatsu
T
T