Interactions between adenosine and nifedipine in the rat cerebral cortex

Nifedipine inhibits the uptake of [³H]adenosine into rat cerebral cortical synaptosomes with an IC₅₀ value of 1.1 μM. When applied by iontophoresis onto rat cerebral cortical neurons it potentiated the depressant effects of adenosine on spontaneous firing. Some of the calcium-antagonist actions of nifedipine may be mediated by adenosine.     

Characterization of adenosine receptor-mediated generation of cyclic AMP in slices of rat cerebral cortex with chronic epileptic activity

Cyclic AMP accumulations elicited by adenosine analogues 2-chloroadenosine (2-CADO),R-N ⁶-phenylisopropyladenosine (R-PIA), andN ⁶-cyclohexyladenosine (CHA) were investigated in cortical slices of chronic iron-induced epileptic rats. Cyclic AMP accumulation was elicited 9-to 18-fold by 2-CADO and it was elicited 5-to 7-fold by eitherR-PIA or CHA; 2-CADO was more potent thanR-PIA or CHA in eliciting cyclic AMP accumulation. The adenosine analogues elicited cyclic AMP accumulation in a dose-dependent manner, and the elicitation was inhibited by the adenosine antagonist 8-phenyltheophylline. The 2-CADO-elicited accumulation of cyclic AMP was greatly increased in the cortical region on the primary epileptic side, while theR-PIA-or CHA-elicited accumulation did not change in any cortical region. The deviation detected only in the 2-CADO-elicited accumulation of cyclic AMP may be due to the difference in relative potency for adenosine receptors of the adenosine analogues. The results suggest that adenosine receptormediated generation of cyclic AMP is altered in the primary region of iron-induced epileptic cortex, in which heterogeneous alterations in different adenosine receptor subtypes may occur in the epileptic process.     

Tissue culture study of unit activity of the rat cerebral cortex

Spontaneous unit activity and morphological characteristics of visual cortical neurons from young rats aged 1 and 2 days were investigated during long-term culture (up to 34 days) of explants in vitro. Three types of spontaneous unit activity were found: single spikes, volleys, and grouped discharges. The types of spontaneous activity were found to depend on the duration of cultivation of the brain tissue. The discharge of single spikes, characteristic of neurons during the first 7–15 days in culture, subsequently was replaced by grouped discharges or volleys of spikes. The changes in unit activity were shown to coincide in time with morphological maturation of the synapses. In experiments in which strychnine (10 µg/ml) was added to the culture medium, a marked increase was observed in the mean frequency of spontaneous unit activity, accompanied by the appearance of discrete series of volley-type discharges. The genesis of spontaneous cortical unit activity is discussed on the basis of these findings.     

Spontaneous electrical activity of the rat cerebral cortex during microwave irradiation

A study was made of changes in spontaneous electrical activity of rat brain cortex induced by a single exposure to microwave radiation (electromagnetic fields of 0.1, 1.0, 10, and 35 mW/cm2). The animals were exposed in anechoic chambers to continuous waves at 2450 MHz in conditions of continuous generation. The data obtained indicate that the EEG parameters change under the effect of microwave radiation. The technique applied permits to study the occurrence and development of the CNS reactions to microwave radiation at the time of action of the factor.     

The maturation of the somatostatin systems in the rat visual cortex

The development of somatostatin-immunoreactive (SS) neurons and processes in the rat visual cortex (VC) was studied in animals from embryonic day 20 (E20) to postnatal day 21 (D21). Three distinct patterns of immunoreactivity were seen. From E20 to birth (D0), VC was characterized by a small number of mainly bipolar SS neurons throughout the cortical plate. In the perinatal period, from D1 to D6, there were large numbers of immature immunoreactive neurons which were confined to layer VI and the subplate zone, a few bipolar neurons in the cortical plate and an extremely dense plexus of SS processes throughout the neuropil. The third phase, from D8 to weaning, was characterized by the absence of immature SS neurons, an increase in the number of multipolar SS neurons and a decrease in the density of SS fibers. By D15, the time of eye-opening, the number and distribution of SS neurons and processes was close to that seen in the adult. These results indicate that the SS system of neurons and fibers is among the earliest of the transmitter systems to be established in VC and suggests a role for the peptide in cortical organization as well as visual processing.     

Regulation of adenosine 3':5'-monophosphate-dependent protein kinase in cerebral cortex

Alterations in the cyclic AMP-dependent protein kinase activity ratio in response to putative neurotransmitters and other cyclic AMP-elevating agents in intact cerebral cortical slices and Krebs-Ringer particulate preparations from cerebral cortex were examined. Both norepinephrine (30 microM) and forskolin (20 microM) produced a time-dependent increase in intracellular levels of cyclic AMP in cerebral cortical slices which was paralleled by an increase in both cyclic AMP and the protein kinase activity ratio. The increases were maximal at 5 min. and remained elevated for at least 15 min. Forskolin, norepinephrine, adenosine and isoproterenol produced a concentration-dependent increase in both cyclic AMP and the protein kinase activity ratio, however, the degree of increase observed was dissimilar. Thus, a 5-fold change in intracellular cyclic AMP resulted in only a 2-fold increase in the activity ratio. Of the agents examined, forskolin produced the most marked change in the activity ratio (from 0.23 to 0.78 at 100 microM) while isoproterenol at 100 microM produced only a 50% increase in the activity ratio. The half-time for the decline in forskolin elicited elevations of either the activity ratio or cyclic AMP was about 4-6 min. In the presence of the phosphodiesterase inhibitor, Ro 20-1724, both were significantly prolonged being 60-70% of the maximum observed immediately after forskolin stimulation, at 15 min. Potentiation of forskolin elicited increases in the activity ratio by Ro 20-1724 were also observed but the increase in the activity ratio was maximal at 7.5 min. while cyclic AMP accumulations continued to rise during the entire 15 min. incubation. Particulate preparations from cerebral cortex were found to contain a cyclic AMP-dependent protein kinase which could be activated 2 to 3-fold with either forskolin, norepinephrine, or adenosine. Unlike the intact brain slice the changes in protein kinase activity ratio and intracellular levels of cyclic AMP in cell-free particulate preparations were similar in both time and degree.     

The diglyceride kinase of rat cerebral cortex

1. Formation of phosphatidic acid by diglyceride kinase (EC 2.7.1.-) in the presence of ATP and Mg(2+) was shown in a homogenate and subcellular fractions of rat cerebral cortex. 2. The kinase was activated by Mg(2+). Ca(2+) activated to a smaller extent but was inhibitory in the presence of optimum concentration of Mg(2+). Activity was greatly increased in the presence of added 1,2-diglyceride. 3. Sodium deoxycholate markedly stimulated the reaction, but other detergents (Cutscum and Triton X-100) did not. 4. Diglyceride kinase was concentrated in the supernatant and microsomal fractions from rat cerebral cortex. The distribution of the kinase in the particulate fractions resembled that of acetylcholinesterase and 5'-nucleotidase. 5. The rate of phosphatidic acid synthesis by the diglyceride kinase route was much greater than reported rates for acylation of 3-glycerophosphate and was also very rapid in comparison with the rates of other steps in the synthesis of phosphoinositides. 6. Acetylcholine had no stimulatory effect on diglyceride kinase of isolated intact nerve-ending particles or of nerve-ending membranes obtained after osmotic shock.     

The small pyramidal neuron of the rat cerebral cortex

Summary The pyramidal neurons in layers II and III of the rat parietal cortex have dendritic spines which form synapses with axon terminals. These synapses have synaptic clefts containing granular material that is concentrated towards the middle of the cleft to form a plaque. Only a small amount of dense material occurs on the cytoplasmic face of the presynaptic membrane, while there is a prominent dense layer, some 300 Å deep, in the dendritic spine. When the synapses formed by the smallest dendritic spines are examined in a frontal or en face plane of section this postsynaptic density has the form of a disc. In the synapses on larger spines, the disc is perforated to form a ring, and in the largest spines a number of perforations may occur. Because of these perforations, in larger synapses sections passing at right angles to the plane of the synaptic junction may show two or more separate postsynaptic densities. The possible significance of these findings is discussed.This work was supported by United States Public Health Service Research Grant No. NB-07016 from the National Institutes of Neurological Diseases and Blindness. The authors wish to express their sincere thanks to Lawrence McCarthy and Charmian Proskauer for their valuable assistance.