The uptake of postulated neurotransmitters of their precursors into regions of the developing chick brain and retina has been examined. The transport of low concentrations (around 10(-8) M) of GABA, glutamic acid, choline, dopamine and serotonin into homogenates was sodium and energy dependent and inhibited by a variety of pharmacological agents that are thought to act presynaptically. After morphological fractionation, the high affinity transport mechanism was concentrated in the nerve ending fraction. Compounds were poorly accumulated by the cerebral regions of the 6 day incubated chick embryo. After this time, the uptake capacity of each brain region studied exhibited a characteristic development profile. Mechanisms for GABA transport appeared early in development, while catecholamine and choline systems matured later. Homogenates of the cerebral hemispheres and optic lobes took up all compounds studied, while the retina and cerebellum of the young chick were able to take up only GABA to a significant extent.

The amount of polyadenylic acid [poly(A)]-containing cytoplasmic RNA in malignant and 'differentiated' mouse neuroblastoma cells in culture was determined. 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), prostaglandin (PG)E1, serum-free medium, X-irradiation and sodium butyrate were used to induce 'differentiation'. The cAMP-induced 'differentiated' cells had more poly(A)-containing cytoplasmic RNA than the malignant cells; the increase in poly-(A)-RNA was greatest in R020-1724-treated cells. The amount of poly(A)-containing cytoplasmic RNA did not significantly change in serum-free medium- or sodium butyrate-treated cells; however, it decreased in cells of confluent phase of growth. The percentage of total radioactive RNA in the cytoplasms of cAMP-induced 'differentiated' cells after 1 h of labeling was three-fold greater than that in malignant cells, indicating that transport of RNA from nucleus to cytoplasm occurs at relatively higher rate in 'differentiated' cells. The stability of RNA in cAMP-induced 'differentiated' cells increased in comparison to malignant cells. The binding of actinomycin D with DNA suggests that the proportion of guanine residues that are accessible to actinomycin D are similar in the nuclei of malignant and cAMP-induced 'differentiated' cells. The present and previous studies suggest that cAMP induces many differentiated functions in neuroblastoma cells by increasing both the transcription and translation of genetic information which is probably masked during malignant transformation of nerve cells. © 1975.

The ability of homogenates of the chick optic lobe to accumulate a series of possible neurotransmitters has been studied. High affinity uptake of several possible neurotransmitters was examined in optic lobes of 21-day-old embryos that had a single eye removed on the third day of incubation and in 23-day-old chicks that had an eye removed at hatch. Embryonic enucleation resulted in severe reduction of development of the ability of the contralateral optic lobe to take up tritiated GABA, dopamine, choline, serotonin and glutamate from solutions around 10(-8)M. Unilateral eye removal of new-hatched chicks caused failure of the denervated optic lobe to grow, but only the uptake capacity for glutamate was significantly recuced. This deficit was apparent as early as 4 days after enucleation. The transport of other compounds was unimpaired. The uptake of glutamate by homogenates of the optic tract was 43% of that or the optic lobe. This was a much greater fraction than the corresponding value for other postulated neurotransmitters. These data suggest that glutamate may be the primary neurotransmitter of the fibers of the optic tract originating in the retinal ganglion cells.

In order to examine muscle ischemia, muscle blood flow in the rat hindlimb was decreased by vessel ligation. Amino acid uptake, studied with [14C]alpha-aminoisobutyric acid, was decreased in ischemic Type I (soleus) muscle. Glucose uptake, studied with [14C]deoxyglucose, was increased in Type I muscle. These changes were temporally associated with histologic changes of ischemia in soleus muscle. Denervation, atrophy, and hypertrophy also produced uptake changes with these techniques, and although more prominent in soleus, the changes were also seen in Type II muscle.

Muscle blood flow, glucose uptake, and the ability of muscle to concentrate an inert amino acid have been studied in vivo using a variety of radiosotopes. The rate of blood flow is four times greater in the slow soleus muscle than in the fast gastrocnemius muscle of the rat, but the rate of deoxyglucose uptake is 14 times higher in the slow muscle relative to the fast muscle. Slow muscle is also able to accumulate the inert amino acid, α-aminoiso-butyric acid, more effectively than does fast muscle. A week after denervation, the rate of blood flow through denervated muscles was increased 30- to 40-fold over control values. However, deoxyglucose uptake was not significantly elevated in the gastrocnemius and was reduced to 20% of control levels in the soleus. The ability of the denervated muscles to concentrate α-aminoisobutyric acid was also impaired. These changes could not be accounted for in terms of an altered inulin space. There is no correlation between the rate of muscle blood flow and the ability of muscle to extract blood-borne nutrients. Impaired transport mechanisms precede and may initiate the major morphological changes that follow muscle denervation. © 1976.