Blood flow and uptake of glucose and amino acids in ischemic muscle.

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.

Development of neurotransmitter uptake in regions of the chick brain.

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.

Putative neurotransmitters of the avian visual pathway.

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.

Axoplasmic transport of RNA containing a polyadenylic acid segment.

The nature of the cytoplasmic RNA that appears to migrate along the optic path of the chick has been studied. A considerable proportion of retinally synthesized RNA contains a polyadenylic acid segment. A fraction of this presumptive messenger RNA moves distally to the optic tectum together with nonpolyadenylic acid-containing RNA. The poly(A)-containing and nonpoly(A)-containing RNA classes are transported in roughly the same proportions as their relative retinal cytoplasmic concentrations. The size of the poly(A) segments within the putative messenger RNA (mRNA) did not decrease with time. A proportion of nonmigrating mRNA in retina and optic tectum appeared to have considerable stability, as did transported mRNA.

Rapid changes in cerebral blood flow and initial visual experience in the developing chick.

A single eye of young chicks was sewed shut for various times. Regions contralateral to and primarily or secondarily innervated by the sutured eye had a reduced rate of cerebral blood flow in comparison to the corresponding ipsilateral regions. However, upon reopening the sutured eye after 2 days, these contralateral regions (optic lobes and cerebral hemispheres) exhibited a rapid increase in cerebral blood flow to a level significantly above that in control ipsilateral areas. The duration of this effect was considerably prolonged in chicks that were monocularly sutured immediately after hatching without prior exposure to light. Chicks that had 1 week of normal vision before monocular suture did not show this overcompensatory effect. If the period of monocular suture was extended to 7 days before restoration of vision to the occluded eye, the overcompensatory vascular effect was delayed. The maximal effect was apparent only upon the 1st exposure of an eye to major visual input. A possible relation exists between this rapid increase in regional blood flow and the period when visual imprinting could normally be expected to be maximal.

Migration of ribosomes along the axons of the chick visual pathway.

The axoplasmic migration of ribosomes has been detected in the visual system of the chick. Monocular injection of radioactive uridine or an amino acid mixture was followed by sedimentation analysis in sucrose or cesium sulfate density gradients, of ribosomes prepared from the retinae of injected eyes and the left and right optic lobes. By this means both RNA and protein components of ribosomes were found to migrate from the retina to the innervated contralateral optic lobe. Following denervation of the distal nerve segment by eye removal, the stability of the transported RNA was reduced, suggesting its presynaptic location. The transport of RNA was not significantly imparied by intraocular injection of inhibitors of informational RNA or mitochondrial RNA synthesis prior to injection of radioactive uridine but was depressed by a low dose of actinomycin D.

Neuroblastoma: drug-induced differentiation increases proportion of cytoplasmic RNA that contains polyadenylic acid.

The production of cytoplasmic RNA that contains polyadenylic acid is increased, relative to total cytoplasmic RNA, in a neuroblastoma clone, NBE-(A), after induction of differentiation by 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, an inhibitor of adenosine 3',5'-monophosphate phosphodiesterase. The amount of RNA that contains polyadenylic acid in cytoplasm may be greater in such differentiated neuroblastoma cells than in proliferating control cells.