Tyrosine hydroxylase activity increases in pineal sympathetic nerves after depletion of neuronal serotonin

Summary The injection of p-chlorophenylalanine (PCPA) acutely reduced serotonin in the pineal gland of the rat and selectively elevated the noradrenaline (NA) content during the subsequent 24 h. The activity of tyrosine hydroxylase (TH) also increased in intact glands during the first 6 h after PCPA injection but returned to normal at 24 h. This enhancement of enzyme activity was only observed in the presence of a non-saturating concentration of the cofactor. Serotonin depletion by PCPA cannot directly account for the increased enzyme activity, because the amine does not modify TH activity. Moreover, this increase is restricted to the pineal, since in other sympathetically innervated organs, such as the atria, PCPA produced an acute but transient reduction in TH activity. The elevation described here is not due to a net increase in the amount of enzymatic protein, because TH activity is similar in pineal homogenates from treated and control rats when a saturating concentration of the cofactor was used. The availability of storage sites in pineal nerve vesicles due to serotonin depletion, seems to release TH activity from the negative control exerted by cytoplasmic catecholamines. Enzyme activity in the pineal is acutely enhanced until a new steady state is reached at a higher concentration of endogenous NA.