Potentiation of bradykinin and eledoisin by BPF (bradykinin potentiating factor) fromBothrops jararaca venom

Zusammenfassung Nachweis der pharmakologischen Wirkung des Bradykinins am isolierten Meerschweinchenileum und am deutlichen Blutdruckanstieg bei Hund und Katze nach Vorbehandlung mit BPF (Bradykinin-potenzierender Faktor aus Jararcagift). Unter diesen Bedingungen werden mit Bradykinin gleich intensive Effekte wie mit Eldoisin erhalten.

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This work was aided by research grants from the Fundação de Amparo à Pesquisa and from the Public Health Service, National Institute of Health, Bethesda (Md. USA) (NB. 02953-03).     

Optical rotatory dispersion of proline-rich peptides from the venom ofBothrops jararaca

Zusammenfassung Die optische Rotationsdispersion mehrer prolinreicher Oligopeptide aus dem Gift der SchlangeBothrops jararaca wurde gemessen und mit jener von Oligoprolinen verglichen. Es konnte nur eine qualitative Beziehung zwischen der angedeuteten Strukturrigidität und der biologischen Wirksamkeit der Peptide festgestellt werden.

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This study was supported by a U.S. Public Health Service Grant No. 1RO1-AM-12473. ProfessorRosalia B. Frydman, Department of Biochemistry, University of Buenos Aires, Argentina, during her visit at Case Western Reserve University, participated in the experiments here reported.     

Inhibition of oxytocin inactivation by some peptides

Zusammenfassung Es wird festgestellt, dass einige peptidische Fragmente des Oxytocins dessen Abbau durch Schwangerenserum, Mäusepankreas und Mäuseleber hemmen.     

The insecticidal potential of venom peptides

Pest insect species are a burden to humans as they destroy crops and serve as vectors for a wide range of diseases including malaria and dengue. Chemical insecticides are currently the dominant approach for combating these pests. However, the de-registration of key classes of chemical insecticides due to their perceived ecological and human health risks in combination with the development of insecticide resistance in many pest insect populations has created an urgent need for improved methods of insect pest control. The venoms of arthropod predators such as spiders and scorpions are a promising source of novel insecticidal peptides that often have different modes of action to extant chemical insecticides. These peptides have been optimized via a prey–predator arms race spanning hundreds of millions of years to target specific types of insect ion channels and receptors. Here we review the current literature on insecticidal venom peptides, with a particular focus on their structural and pharmacological diversity, and discuss their potential for deployment as insecticides.     

Inhibition by transmembrane peptides of chimeric insulin receptors

Receptor tyrosine kinases play essential roles in cell proliferation and differentiation. We have recently shown that peptides corresponding to the transmembrane domains of the epidermal growth factor (EGF) and ErbB2 receptors inhibit their corresponding receptor activation in cancer cell lines. We extend this observation to cells transfected with chimeric insulin receptors where the transmembrane domain has been replaced by that of the EGF receptor or a mutated Erb2 domain. Peptides corresponding to the transmembrane domains of the EGF receptor and ErbB2 are able to inhibit specifically the autophosphorylation of insulin receptors with the corresponding domain. This inhibitory effect is correlated with the propensity of the different transmembrane domains to self-associate in a genetic reporter assay. Thus, our data strengthen the notion that transmembrane domains are involved in erbB receptor activation, and that these receptors can be modulated by inhibiting proteinprotein interactions within the membrane.Received 25 May 2005; received after revision 13 July 2005; accepted 22 July 2005     

Cleavage of active peptides by a lung enzyme

Zusammenfassung Ein Enzym (Angiotensin I «converting enzyme» oder Kininase II; DH) wurde aus Schweinelungen isoliert und gereinigt. DH splatet Dipeptide vom Carboxyterminus der Peptidsubstrate mit Einschluss von Bradykinin, Angiotensin I, B-Kette von Insulin und¹⁴C-DNS-Gly-Gly-Gly. Zu den besten Inhibitoren des Enzyms gehören zwei kürzlich synthetisierte Peptide sowie Glutathion und Insulin. Die Experimente deuten auf ein einziges Enzym hin, das alle erwähnten Substrate hydrolysiert.

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Supported in part by grants No. HE 08764 and No. 5T01 HE 05859 from N.I.H., U.S.P.H.S. and by the O.N.R. No. N00014-68-A-0496 and No. N00014-69-A-0385.

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During the tenure of a fellowship of the Oklahoma Heart Association.

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Acknowledgements. MissDeborah Downs assisted us in some of the experiments. HHL was donated by Dr.D. Cushman of the Squibb Institute.     

Studies on the hydrolysis of bradykinin by angiotensin-converting enzyme (kininase II)

Summary Arg-Pro-Pro-Gly-Phe, the N-terminal pentapeptide of bradykinin, is not an inhibitor of angiotensin-converting enzyme and is not hydrolyzed by the enzyme. Arg-Pro-Pro, the N-terminal tripeptide is a relatively potent (IC₅₀=2.3×10⁶ M) inhibitor but its higher homolog, Gly-Arg-Met-Lys-Arg-Pro-Pro is not an inhibitor of angiotensin-converting enzyme.This work was supported in part by grants from the US Public Health Service (HL 18415, HL 15691, HL 19764) and the John A. Hartford Foundation, Inc., and by the Medical Research Service of the Veterans Administration.     

Release of bradykinin as related to the esterase activity of trypsin and of the venom ofBothrops jararaca

Zusammenfassung Die proteolytische Aktivität des Giftes vonBothrops jararaca wird durch Erhitzen leicht zerstört und dabei eine Esterase mit grösserer Hitzeresistenz abgetrennt. Nach Hitzefraktionierung des Giftes steht die Aktivität dieser Esterase in direktem Verhältnis zum abgegebenen Bradykinin und zur Gerinnung des frischen Plasmas.     

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1–7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1–7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.     

Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin

Summary Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E₂ in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastrointestinal activities reflecting duration of availability rather than receptor affinity.The author acknowledges the technical assistance of Mr L. Chamberland, Miss A. Colaviti and Miss C. Pilapil.     

Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin.

Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E2 in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastro-intestinal activities reflecting duration of availability rather than receptor affinity.     

Influences of the chemical structure on the activity of new inhibitory compounds of the angiotensin-converting enzyme

Summary The ACE inhibitory activity of some perimidines, chinazolinones and amidinohydrazones is described. Relations were found between the chemical structure and the inhibitory activity on the ACE.     

Influences of the chemical structure on the activity of new inhibitory compounds of the angiotensin-converting enzyme

The ACE inhibitory activity of some perimidines, chinazolinones and amidinohydrazones is described. Relations were found between the chemical structure and the inhibitory activity on the ACE.