Effect of 6-hydroxydopamine on daily variations of 5-HT synthesis in the hypothalamus of the rat

In the cortical gray matter of human brains, which were obtained by permissible resection at the time of surgery, cyclic 3′, 5′-AMP was found in a range of concentrations between 42 and 143 pmole/mg protein. The subcortical white matter and various types of brain tumor contained much lower concentrations of the nucleotide. The level of the cyclic nucleotide in incubated slices of gray matter was elevated 20–50-fold by norepinephrine (0.5–1.0 mM) or veratridine (0.05 mM), 4–7-fold by histamine (1.0mM) or adenosine (0.2mM) and 1.5–2-fold by serotonin. With respect to the stimulatory effect on the cyclic AMP level in human brain slices, norepinephrine was inferior to epinephrine or isoproterenol, and was completely antagonized with a β-adrenergic blocking agent, propranolol, but only slightly by α-blocking agents, such as phentolamine and dibenamine.The particulate fraction of human brain homogenate was capable of synthesizing cyclic AMP from ATP. This enzymic activity was 0.19–0.24 nmole/min/mg protein. This activity was stimulated 2–3-fold by the addition of 10mM NaF but not by any of the biogenic amines tested. The activity of nucleotide phosphodiesterase of human brain was almost equal to that of rat brain: only a single K_m for the substrate cyclic AMP was observed around 0.9 × 10^?4M.