Susceptibility of neuroactive peptides to aminopeptidase digestion is related to molecular size.

Peptide fragments derived from the NH₂-terminus of corticotropin were found to exhibit widely differing degrees of stability to degradation by aminopeptidase M. Corticotropin itself was 135 times more stable than its NH₂-terminal pentapeptide, and similar differences in stability were observed with peptides derived from the B-chain of bovine insulin. Enkephalin linked covalently to the A-chain of bovine insulin was at least 100 times more stable than the pentapeptide. The results demonstrate that the molecular size of a peptide is one factor that determines its NH₂-terminal stability.     

Electroencephalographic changes in the lateral septum complex following systemic administration of DES-TYR1 -α-endorphin,Des-Tyr1-γ-endorphin and haloperidol in rats

The influence of systemically administered Des-Tyr¹-α-endorphin (DTαE), Des-Tyr¹-γ-endorphin (DTγE) and haloperidol on electroencephalographic (EEG) activity of the lateral septum complex (LSC) and the frontal cortex was studied in male rats. DTαE (2 μg) significantly increased whereas DTγE (10 μg) significantly decreased the amounts of activity in the 5 Hz band. In addition, DTαE promoted production of 15 - 20 Hz activity, while DTγE decreased the amount of 20 - 30 Hz activity. EEG activity exhibited a marked variability which persisted throughout the recording session following administration of the peptides. Haloperidol markedly decreased the proportion of 10 - 15 Hz activity. The alterations in EEG of the frontal cortex were similar to those in LSC but less pronounced. The differences in the time course and frequency bands affected suggest that the effects of peptides and haloperidol on EEG activity of LSC are not mediated by the same mechanisms.     

Acyltransferase-catalyzed cleavage of arachidonic acid from phospholipids and transfer to lysophosphatides in lymphocytes and macrophages

The cleavage of fatty acyl moieties from phospholipids was compared in intact cells and homogenates of mouse lymphocytes (thymocytes, spleen cells) and macrophages. Liberation of free arachidonic acid during incubations of intact cells was only detectable in the presence of albumin. Homogenization of prelabeled thymocytes and further incubation of these homogenates at 37 degrees C resulted in a pronounced decrease of phospholipid degradation and cleavage of arachidonoyl residues, while further incubation of homogenates from prelabeled macrophages produced a greatly increased phospholipid degradation. Homogenates of macrophages but not those of thymocytes contain substantial activities of phospholipase A2 detectable using exogenous radiolabeled substrates. These findings indicate that in thymocytes cleavage of arachidonic acid from phosphatidylcholine is an active process that is not catalyzed by phospholipase A2. Addition of CoA and lysophosphatidylethanolamine to prelabeled thymocyte homogenates induced a fast breakdown of phosphatidylcholine and transfer of arachidonic acid to phosphatidylethanolamine, as in seen during incubations of intact thymocytes or macrophages. The transfer is restricted to arachidonic acid and does not require addition of ATP. Sodium cholate, a known inhibitor of the acyl-CoA:lysophosphatide acyltransferase, completely inhibited this transfer reaction. These results suggest that the CoA-mediated, ATP-independent breakdown of phosphatidylcholine and transfer of arachidonic acid is catalyzed by the acyl-CoA:lysophosphatide acyltransferase operating in reverse.     

Biochemical, biological, and immunological properties of chemically deglycosylated human choriogonadotropin

A chemical method of deglycosylation of human choriogonadotropin (hCG) was used to assess the role of carbohydrate moiety in the maintenance of quaternary structure and functional parameters such as receptor binding, immunological activity, and in vitro biological response. Treatment of purified hCG with anhydrous HF at 0 degrees C for 60 min was effective in removing more than 75% of the carbohydrate moiety. This extent of deglycosylation altered its chromatographic characteristics as revealed by retarded behavior on Sephadex G-100 and failure to be retained on concanavalin A-Sepharose. The electrophoretic heterogeneity present in native hCG was markedly reduced by deglycosylation. The deglycosylated hCG was stable in the lyophilized form and retained its quaternary structure as revealed by the fluorescence probe 8-anilino 1-naphthalene sulfonic acid, receptor binding, and immunological activities. Unlike receptor binding and immunological activities, which were fully retained, the ability of the hormone to stimulate cyclic AMP accumulation in vitro in rat interstitial cells was completely abolished.     

Prolonged alteration in composition of fast transported protein in axons prevented from regenerating after injury

A previous study revealed a characteristic alteration in the ratio of labeling of two fast axonally transported polypeptides identified as S1 (22,000 daltons) and S2 (18,000 daltons) and their ratio (S2/S1) in rat motoneuron axons following axonal injury and subsequent regeneration. In this study the S2/S1 ratio was determined for axons which were resected and ligated proximally and which did not regenerate to reinnervate muscle. While the initial increase in the S2/S1 ratio following section was the same as that following a crush, the S2/S1 ratio did not return towards normal values after 42 days, but remained elevated for at least 98 days after injury. It is concluded that the return of S2/S1 ratio to normal values, like some other manifestations of the cell body reaction, is delayed if the injured axons do not regenerate.     

Glycoproteins of trypanosomes: their biosynthesis and biological significance

1. Trypanosomes are unicellular parasites that cause human sleeping sickness in Africa and Chagas' disease in South America. Glycoproteins are important components of their plasma membrane. 2. The bloodstream form of the extracellular salivarian African trypanosome (e.g. Trypanosoma brucei) has the ability to express on its cell surface a repertoire of variant surface glycoproteins (VSGs) and in so doing, evades the immune response of the host (antigenic variation). 3. The VSG is probably synthesized initially in a manner like that of the membrane-bound glycoproteins of mammalian systems, but it also undergoes some novel post-translational modifications. 4. The stercorarian South American trypanosome (Trypanosoma cruzi) is an intracellular parasite which expresses different glycoproteins on its plasma membrane at various stages of its life-cycle, but does not exhibit antigenic variation. 5. The biosynthesis and functions of trypanosomal glycoproteins are compared with those of mammalian glycoproteins, and are discussed with particular reference to potential targets for chemotherapy and immunotherapy of trypanosomiasis.