Activation of hypolipidaemic drugs to acyl-coenzyme A thioesters.

Compounds possessing the characteristics of CoA thioesters of the hypolipidaemic peroxisome proliferators clofibric acid, nafenopin and ciprofibrate were formed on incubation of the drugs with rat liver microsomal fractions, ATP and CoA. The reactivity of the drugs correlated with their pharmacological potency. It is proposed that the active species of these compounds are their acyl-CoA thioesters.     

Stimulation of Free Fatty Acid and Diacylglycerol Accumulation in Cerebrum and Cerebellum During Bicuculline-Induced Status Epilepticus. Effect of Pretreatment with α-Methyl-p-Tyrosine and p-Chlorophenylalanine

The pool size and composition of free fatty acids (FFA) and diglycerides (DG) from the cerebrum and cerebellum of rats undergoing bicuculline-induced seizures were studied. A fourfold increase in cerebral FFA occurred 3-4 min after bicuculline injection; arachidonic and stearic acids were the principal fatty acids accumulated. Cerebellar FFA also increased, but to a lesser extent. An increased production of arachidonic acid took place in the cerebrum as a function of time after bicuculline injection. Other fatty acids produced were oleic, palmitic, and docosahexaenoic acids. A twofold increase in cerebral arachidonic acid was seen at the time of the first generalized tonic-clonic convulsion. However, a 13- to 17-fold increase in arachidonic acid was seen approximately 5-6 min after bicuculline injection. The rise in other FFA was much smaller. Stearoyl- and arachidonoyl-DG were also accumulated. The drug alpha-methyl-p-tyrosine was found to (a) potentiate the bicuculline-stimulated release of cerebellar FFA, and (b) inhibit by 70% the production of stearoyl- and arachidonoyl-DG in the cerebrum and cerebellum. Basal production of FFA was stimulated by p-chlorophenylalanine, but the drug had no effect on the bicuculline-induced changes. Hydrolysis of phospholipids enriched in stearoyl-arachidonoyl groups, such as phosphatidylinositol of excitable membranes, may be stimulated during seizures.     

Succulence and CAM relationships in Aeonium genus

The CAM has been tested in six species of the Aeonium genus by studying the diurnal fluctuation of organic acids, pH and night fixation of CO₂. The existence of a mesophyll structure able to support this metabolism has been shown as well as a congruent periodicity in the pool of cell starch. We have calculated the S, ES and Sm indices in the six species. A series of regression equations of different grades and types were calculated and shown to have correlation coefficients statistically significant. This allows us to confirm the suitability of the Sm index as a rapid test to establish the CAM as postulated by former authors.     

Protein kinase from Mucor rouxii

Summary Cyclic AMP binding to Mucor rouxii protein kinase holoenzyme and free regulatory subunit was measured by the classical membrane filtration technique and by equilibrium dialysis. The results obtained demonstrate that the filtration method can be used without loss of any cyclic AMP binding site. Both methods unambiguously demonstrate that the number of molecules of cyclic AMP bound to the holoenzyme are half of those bound to the regulatory subunit. This result suggests that unshielding of new cyclic AMP binding sites occurs upon dissociation of the ternary complex holoenzyme-cyclic AMP.     

Extracellular action potentials recorded from the interior of the giant esophageal cell of Ascaris

Exploration of the cytoplasm of the giant esophageal cell of Ascaris with a recording microelectrode shows the existence of shallow spaces where the microelectrode tip becomes extracellular in spite of being in the interior of the cell. When the microelectrode penetrates into these spaces from the cytoplasm, the resting potential shifts to a different level or entirely disappears. At the same time the large intracellular spikes are replaced by small transients similar to extracellularly recorded action potentials. It is concluded that such spaces are in communication with the external solution, and separated from the cytoplasm by an electrically active membrane; i.e., able to generate action potentials. Measurement of the potential differences between the interior of the spaces and the external solution shows that although some are not polarized, many spaces have a resting potential of the same polarity as that of the cytoplasm. It is suggested that although they are of larger size these spaces may be equivalent to the tubular systems which in other muscle cells are known to be involved in the spread of excitation into the cytoplasm.     

Influence of Some Ions on the Membrane Potential of Ascaris Muscle

The influence of several ions on the membrane potential of the somatic muscle of Ascaris has been investigated by changing their concentration in the surrounding solution. When [K]_o is increased at the expense of [Na]_o leaving [Cl]_o constant, the membrane potential is first seen to increase. [K]_o higher than 45 mM reduces the membrane potential with a slope of 23 mv for a tenfold change in [K]_o. However, when [K]_o is increased keeping [Na]_o and [Cl]_o low and constant, the line relating the membrane potential with log [K]_o has a slope of almost 50 mv. If [Cl]_o is reduced in the absence of external Na, after the [K]_o is increased to 45 mM, the membrane potential decreases with a slope of 59 mv per tenfold change in [Cl]_o in close agreement with the Nernst equation. If Cl^- is replaced by SO₄ ^2-, a depolarization is produced, while chloride replacement by NO₃ ^-, Br^-, and I^- results in a hyperpolarization of the membrane. Removal of the external Na⁺ ions increases the average membrane potential by 17 mv.     

Acetylcholine sensitivity of the spine-test articular capsule of the sea urchin Eucidaris tribuloides

1. The changes in the consistence of the spine-test articular capsule, or ligament, of the primary spines of Eucidaris tribuloides induced by acetylcholine (ACh) have been studied. Two complementary techniques were used: (a) "forced-vibration", which detects variations in the stiffness of the ligament along a single diametral plane; and (b) "forced-rotation" which records the spatial distribution of those changes. 2. ACh (1 microM to 1 mM) caused a rapid increase in the resistive force opposed by the ligament to passive stretching. Similar effects were elicited by several monoquaternary, N-substituted derivatives of trimethylammonium. 3. The opposite effect, i.e. softening, was induced by decamethonium, dimethylphenylpiperazine, and 2-ketoamyltrimethylammonium. 4. The involvement in these effects of ACh-binding groups with pharmacological properties similar to those of the "anionic sites" of nicotinic ACh receptors is suggested.