IN VIVO CHANGES OF CEREBRAL CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE INDUCED BY BIOGENIC AMINES: ASSOCIATION WITH PHOSPHORYLASE ACTIVATION

Abstract

The intravenous injection of adrenaline, isoprenaline and histamine to 4-6-day-old chicks resulted in a rapid increase in the cyclic AMP content of cerebral hemispheres that had been removed and frozen within 0.5 s using a freeze-blowing technique. Noradrenaline, dopamine, adenosine, 5-HT and acetylcholine did not significantly alter the nucleotide concentration in uiuo. Addition of adrenaline, isoprenaline and histamine to incubated chick cerebral cortex slices also increased the cyclic AMP content of the tissue. Noradrenaline was considerably less potent than these amines and adenosine was ineffective.Low phosphorylase a levels (16 per cent of total activity) were observed in instantaneously frozen cerebral hemispheres of untreated chicks. The injection of adrenaline, isoprenaline and histamine resulted in a rapid conversion of phosphorylase b to a and a significant fall in tissue glycogen. Administration of noradrenaline was without effect on the relative forms of phosphorylase and also failed to influence cerebral glycogen. Phosphorylase activation was not observed in chick cerebral slices under conditions prod Ycing large increases in cyclic AMP.It is suggested that in uiuo phosphorylase -activation and subsequent glycogenolysis may occur, at least in part, in glia and that these cells may be damaged during preparation of cerebral slices. The results provide evidence of a metabolic role for cyclic AMP in cerebral tissue.

Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism.

“…In our studies, the effect ofVIP also was potentiated by isobutylmethylxanthine (not shown), suggesting that the glycogenolytic action of the peptide was mediated by cyclic AMP. In peripheral tissues (52), brain (23,24), neuroblastoma, and astrocytoma cell lines (25,26), cyclic AMP activates phosphorylase through a cascade of enzymatic phosphorylation steps, thus initiating glycogen degradation. This process, along with the inhibition of glycogen synthetase (26), ultimately results in a decrease in the cellular glycogen content.…”

“…A large number of studies have been published with regard to the various aspects of glycogen metabolism in glial and neuronal elements (23)(24)(25)(26)(27)(28). Furthermore, in a series of elegant biochemical and autoradiographic studies, Wolfe and Nicholls (29) have shown that a mechanism for ['4C]glucose uptake and the subsequent synthesis of ['4C]glycogen existed in glial cells and neurons of the leech central nervous system.…”

H-2 Histamine Receptors

“…Though the hypothalamus contains the most histamine in all species, in most of these histamine does not increase cAMP and excites rather than inhibits hypothalamic neurons, being inhibi tory to most other neurons. In the chicken brain, cAMP stimulation by histamine is blocked by metiamide (189) and not potentiated by adenosine (190). In guinea pig cerebral cortical or hippocampal slices, histamine effects are partly (50-80%) blocked by either H-1 or H-2 antagonists while both together completely block the response (186).…”

Stimulation of Carbonic Anhydrase Activity and Phosphorylation in Primary Astroglial Cultures by Norepinephrine

“…The activities of a few other nervous system enzymes have been shown to be associated with stimulation of cAMP levels. Brain glycogen phosphorylase activity is increased by agents that stimulate 3',5'-cyclic AMP levels (Edwards et al, 1974). Tyrosine hydroxylase purified from rat caudate nucleus incorporated 32P when incubated with a CAMP-dependent protein kinase in vitro, and a twofold increase in enzyme activity was also obtained (Joh et al, 1978).…”