Characterization of VIP-sensitive adenylate cyclase in guinea pig brain

This paper demonstrates that VIP activates an adenylate cyclase from a synaptosomal fraction of guinea pig brain. This activation was not potentiated by guanyl triphosphate nucleotides, and was unaffected by α- and β-adrenergic blockers and by atropine. Furthermore, peptides related to VIP, like secretin, glucagon and somatostatin, were devoid of significant agonistic or antagonistic activity. EGTA was also without effect on basal and VIP stimulated activities while calcium at concentrations higher than 10-5 M inhibited both activities.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The interaction of caerulein with the rat pancreas. II. Specific binding of [3H]caerulein on dispersed acinar cells

1. [3H]Caerulein was bound to dispersed acinar cells from rat pancreas in a rapid, reversible, specific, saturable, and temperature-dependent manner. Binding decreased above pH 6.5. Treatment of intact cells with 2, 4-dinitrophenol and oligomycin, p-choloromercuribenzoate, diisopropylfluoro-phosphate and glutaraldehyde impaired [3H]caerulein binding whereas the addition of EGTA inhibited binding. The C-terminal octapeptide of pancreozymin, desulfated caerulein and pentagastrin inhibited binding of [3H]caerulein whereas vasoactive intestinal polypeptide, secretin, bombesin or carbamoylcholine were wothout effect. The good resistance of [3H]caerulein to inactivation by acinar cells at 37 degrees C was reflected in the high proportion of tracer remaining capable of binding to fresh acinar cells. 2. Scatchard plots of [3H]caerulein binding were curvilinear with an upward concavity. The addition of an excess of unlabeled caerulein resulted in the release of as much as 65% of bound [3H]caerulein within 1 min at 37 degrees C. The dissociation of remainder followed much slower kinetics. 3. The results suggested that intact rat pancreatic acinar cells have one class of caerulein binding sites existing in two states: one with high affinity and another with low affinity, the proportion of sites in each state depending on the degree of site occupancy (negative cooperativity), and on the intracellular concentration of nucleotides.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Demonstration of biological activity of brain gastrin-like peptidic material in the human: its relationship with the COOH-terminal octapeptide of cholecystokinin.

The previously described peptide material that reacts with antibodies to gastrin and is found in the central nervous system of various vertebrates is present in only the 100,000 X g pellet of postmortem human cerebral cortical grey matter. This immunoreactive material, extractable in boiling water, is biologically active on rat pancreatic preparations. On the basis of size, charge, immunological specificity, and patterns of biological activity, most of this material is closely related to the COOH-terminal octapeptide of cholecystokinin in its complete, sulfated biologically active form

Technological learning, technological substitution, and technological change

From a simple dynamic model of competition between product lines it is shown that the shape of learning curves has a powerful influence on the dynamics of technological substitution. Learning of both production efficiency and marketing efficiency is considered. It is asserted that both types of learning are important and that the two are complementary. It is further speculated that production learning is probably more important for commodities and in situations of low per capita income, whereas market learning gains ascendancy in cases of high income and specialized and diversified product lines. In closing, it is noted that simple competitive models are misleading, first because complementarities and coevolutionary processes are probably as important in the overall development of technology as are competitive processes, and second because optimization of the technological system's parts does not guarantee improvement of the performance of the system as a whole

ANP is degraded by activated neutrophils

XXXIInd Annual Congress of the European Dialysis and Transplant Association (Athens, Greece, June 11-14, 1995)info:eu-repo/semantics/publishe

Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat.

The metabolism of atrial natriuretic peptide (ANP) and Cys-105-Phe-106-cleaved ANP (ANP) was studied during constant infusion of 125I-labelled peptides in rats. Analysis of circulating radioactivity indicated rapid clearance of ANP and ANP', with mean half-lives of 0.42 and 1.04 min respectively. H.p.l.c. fractionation of plasma taken during the infusion of labelled ANP revealed the presence of three radioactive fragments, the major one co-eluting with 125I-ANP'. These fragments correspond to cleavage products previously found to be generated in vitro by the action of endopeptidase 24.11 (E-24.11). On evaluating the effects of peptidase inhibitors, a significant increase in the half-life of ANP was observed with phosphoramidon (t1/2 7.8 min) and aprotinin (t1/2 5.4 min). A maximal inhibition of ANP degradation was obtained when both inhibitors were given simultaneously (t1/2 15 min). In blood samples taken during infusion of 125I-ANP and phosphoramidon, the intact peptide accounted for more than 90% of total circulating radioactivity, and no cleavage product was present in detectable amounts. Phosphoramidon had no effect on the metabolism of infused ANP'. In contrast, when 125I-ANP' was infused together with aprotinin, the rate of degradation of the infused peptide was reduced by more than 80%. It is proposed that two different peptidase activities, E-24.11 and a kallikrein-like proteinase, are responsible for the cleavage of ANP in the circulation. The Cys-Phe-cleaved ANP would in turn be degraded by kallikrein and not by E-24.11

Urinary neutral endopeptidase in workers exposed to cadmium: interaction with cigarette smoking.

OBJECTIVES: Structural impairment of the renal proximal tubular epithelium induced by cadmium (Cd) was investigated by measuring the concentration of neutral endopeptidase 24.11 (NEP), an ectoenzyme of the apical brush border, in the urine of 106 male workers employed in a Cd smelter (among whom 52 were occupationally exposed to Cd), and by comparing it with other tubular markers (low molecular weight proteins, lysosomal enzymes). METHODS: NEP (EC 3.4.24.11), beta-N-acetyl-glucosaminidase (NAG) (EC 3.2.1.30), and NAG-B isoenzyme activities were measured by fluorimetric assays, whereas the concentrations of retinol binding protein (RBP), beta 2-microglobulin (beta 2M), and Clara cell protein (CC16) were measured by automated latex agglutination techniques. RESULTS: An increased urinary excretion of NEP as well as microproteins was found only in subjects excreting more than 5 micrograms Cd/g creatinine. In this group, NEP concentrations were significantly higher in the subjects who smoked. This significant interaction could not be found for any other marker tested. CONCLUSIONS: The data suggest that NEP enzymuria is high even at low exposures to Cd (with a threshold of urinary cadmium excretion (U-Cd) at 5 micrograms/g creatinine), indicating early structural alterations. Moreover, its particular sensitivity to smoking could be useful in the detection of new population clusters potentially more susceptible to development of nephrotoxic insult