Snake venom action: Are enzymes involved in it?

Summary Enzymes were the first clearly recognized components of snake venoms. When several more were discovered, attempts were made to correlate venom action with enzymic functions. The last few years have seen most successful efforts in the identification, isolation and structural elucidation of highly toxic polypeptides present in snake venoms, in particular of neurotoxins and membrane-active toxins. Following this development the polypeptides were called the true toxic components and the enzymes lost their previous central position in venom pharmacology. The time, therefore, has come to re-evaluate the role of enzymes in the complex interaction between snake and prey. While highly active polypeptides indeed dominate the action of hydrophiid venoms, they appear to play a lesser role in crotalid venom action as compared with enzyme components. Enzymes are involved in many levels of venom action, e. g. by serving as spreading factors, of by producing very active agents, such as bradykinin and lysolecithins in tissues of preys or predators. Some toxins, e. g. the membrane-active polypeptides appear to participate in the interaction between membrane phospholipids and venom phospholipases. The classical neurotoxin, -bungarotoxin, has been recognized as a powerful phospholipase. Several instances are known which indicate that some enzymes potentiate the toxic action of others; the analysis of a single enzyme may, therefore, not fully reveal its biofunction. For 3 enzymes, ophidianl-amino acid oxidase, ATPpyrophosphatase, and acetylcholinesterase, some of the problems pertaining to venom toxicity are discussed.     

Species difference in the effects of proteolytic enzymes on red cell membrane

Summary Pronase and -chymotrypsin digested the major glycoprotein in the human and mouse red cell membranes and in SDS gel electrophoresis the glycoprotein disappeared accompanied by the appearance of a new band of lower mol.wt. However in the membranes of sheep, rat and rabbit, no digestion was demonstrated. The effects of pronase on anion permeability were almost identical for human and animal erythrocytes.     

Irreversible shock in rats after injection of microspheres into the renal artery

Summary After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4–12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.These studies were supported in part by the Deutsche Forschungsgemeinschaft within the SFB 90, Cardiovasculäres System.     

N-(5′-Phosphopyridoxyl)-4-aminobutyric acid: a stable bisubstrate adduct inhibitor of rat brain 4-aminobutyric acid aminotransferase

Summary N-(5-Phosphopyridoxyl)-4-aminobutyric acid, a stable adduct of pyridoxal phosphate and 4-aminobutyric acid, has been shown to be a potent inhibitor of rat brain 4-aminobutyric acid aminotransferase (GABA-T) with a K_i of 1.4 M.Acknowledgments. This work was supported in part by the United Parkinson Foundation, l'Association Canadienne l'Ataxie de Friedreich, and the Medical Research Council of Canada.     

A cannabinoid with cardiovascular activity but no overt behavioral effects

Summary Abnormal-⁸-tetrahydrocannabidiol (ABN-⁸-THC) failed to elicit central nervous system and cardiovascular effects in laboratory animals. Abnormal-cannabidiol (ABN-CBD) was also devoid of overt behavioral effects but produced marked hypotension with only slight bradycardia in anesthesized dogs.Acknowledgment. This work was supported by NIDA (grant No. DA-00574-01 and DA-00490) and Virginia Heart Society (grant No. RR-05697)     

A tissue-selective prostaglandin E2 analog with potent antifertility effects

Summary N-methanesulfonyl 16-phenoxy--tetranor PGE₂ is a prostaglandin analog which is markedly more tissue selective than PGE₂. This compound is 10–30 times more potent than PGE₂ in animal models which are considered relevant to antifertility effects in humans. In pharmacological tests which are believed to be predictive for side effects in humans, the compound has potency either equal to or less than that of PGE₂.     

Determinant selection is a macrophage dependent immune response gene function

Immune response (Ir) genes are linked to the species histocompatibility complex and define as yet uncharacterised phenotypic products which control the immune response to thymus dependent antigens. Antibody formation and antigen induced T lymphocyte proliferation are two examples of immune phenomena which, in vivo and in vitro, operate under Ir gene influence. To clarify their mechanism of action and cellular location, we have examined the contribution of antigen structure (amino acid sequence and conformation to Ir gene control of antigen recognition by T lymphocytes) as well as to the critical role played by the antigen presenting macrophage in expression of that control. We report that immune response gene control of antigen recognition operates at least in part at the level of the macrophage.     

Antioxidant effects on prostaglandin synthesis in rabbit kidney medulla slices

Summary Sodium diethyldithiocarbamate, 2,6-di-tert-butylphenol and N,N-diphenyl-p-phenylenediamine inhibited the generation of medullary prostaglandin E, but 1,2-dimethoxyethane (OH scavenger) and 2,5-dimethylfuran (¹O₂ scavenger) stimulated basal prostaglandin E production 1.2–1.3-fold. These results suggest that the balance between formation and removal of cellular lipid peroxides sets a peroxide level that can regulate the rate of prostaglandin formation in cells.     

Survival and endogenous spleen colonies of irradiated mice after skin wounding and hydroxyurea treatment

Summary Wound trauma-induced survival from radiation may be related to increased mitosis in hematopoietic cells. This is supported by the cell cycle-dependent drug hydroxyurea, which 1. blocked survival of wounded mice injected 2 or 3 days after 900 rad and 2. reduced the number of endogenous CFU-s in wounded mice injected shortly before 700 rad.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under Research Work Unit MJ00018. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should be inferred.Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Research, National Research Council.