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J Martinez

Publications and source records attributed to J Martinez.

At least 361 records · Page 20Linked to original sources
PubMed1990

Changes in brain neuropeptide Y induced by cholecystokinin peptides.

Cholecystokinin (CCK) and neuropeptide Y (NPY) are two peptides with opposite effects on the regulation of feeding behaviour. The possible interaction between these two systems has always been controversial. In this study, rat brain NPY levels were assayed after treatment with CCK 8 S and with a potent CCK agonist (Boc-(Nle 28-Nle 31)-CCK 26-33). CCK 8 S and its agonist analogue (50 micrograms/kg i.p.) both decreased hypothalamic and hippocampal NPY levels. This result suggests a negative relationship between NPY and CCK-peptides which is not surprising given their opposite role in the control of feeding. The hypothalamus and secondarily the hippocampus appear to be the site of this interaction; no change in NPY levels was observed in other brain areas (striatum and cortex). The same pattern of variation was found in the plasma, suggesting a direct release from the brain via a mechanism which remains to be investigated. The effect appeared later with the CCK analogue than with CCK 8 S itself; this is not surprising with regard to other behavioural and biochemical effects of the analogue and provides further characterization of its action.

Animals↗
PubMed1990

Effects of a new cholecystokinin analogue (JMV 236) on food intake and brain monoamines in the rat.

JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.

Animals↗
PubMed1990

Correlation between phospholipid breakdown, intracellular calcium mobilization and enzyme secretion in rat pancreatic acini treated with Boc-[Nle28, Nle31]-CCK-7 and JMV180, two cholecystokinin analogues.

In this work in vitro pharmacological profiles of two analogues of the C-terminal heptapeptide of cholecystokinin (CCK) were evaluated. The analogue Boc-[Nle28, Nle31]-CCK-7, a stable analogue of CCK-8, has the same activity profile as CCK-8, and was found to be very potent in stimulating amylase secretion, phospholipid breakdown and [Ca2+]i mobilization from rat pancreatic acini. It can be used as a probe for studying CCK-actions. The CCK-analogue Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester, (JMV180), which stimulates amylase secretion without inhibition at supramaximal concentrations, has different effects on phospholipid hydrolysis and [Ca2+]i mobilization, compared to CCK-8 and Boc-[Nle28, Nle31]-CCK-7. Compound JMV180 was unable to significantly promote phospholipid breakdown, and was only 50%-60% as efficacious as Boc-[Nle28, Nle31]-CCK-7 in promoting [Ca2+]i mobilization. These findings suggest that low affinity CCK-receptors might be responsible for the supra-maximal inhibition of amylase secretion, and are correlated with phospholipid breakdown and maximal [Ca2+]i mobilization.

Amylases↗
PubMed1990

Binding and covalent processing of fibrinogen by hepatocytes and endothelial cells.

In contrast to most plasma glycoproteins, asialofibrinogen and aglycofibrinogen manifest relatively normal in vivo survivals, suggesting that molecular determinants other than the carbohydrate may be involved in their catabolism. To analyse the metabolic properties of fibrinogen further, we analysed the interaction of normal fibrinogen with suspensions of rabbit hepatocytes or human umbilical vein endothelial cells. In so doing, we identified a novel type of fibrinogen - cell interaction which has the distinguishing characteristic of involving covalent transglutaminase-mediated fibrinogen cross-linking. In this report, we highlight some of the major distinguishing characteristics of this novel type of transglutaminase-mediated fibrinogen - cell interaction.

Animals↗
PubMed1990

Synthesis of cyclic analogues of cholecystokinin highly selective for central receptors.

Cyclic CCK analogues in which positions 28 and 31 have been replaced by lysine residues and whose side chains are bridged by a succinic moiety, were synthesized. They were tested for their ability to inhibit the binding of 125I-BH-CCK-8 to isolated rat pancreatic acini and to guinea pig brain membranes. These cyclic CCK-analogues were compared to the potent CCK analogue Boc-[Nle28,31]-CCK-7 and to Boc-Trp-Leu-Asp-Phe-NH2, analogue of CCK-4. These cyclic compounds appeared to be highly selective for central CCK receptors.

Amino Acid Sequence↗
PubMed1990

Neuroblastoma differentiation involves the expression of two isoforms of the alpha-subunit of Go.

The regulation of GTP-binding proteins (G proteins) was examined during the course of differentiation of neuroblastoma N1E-115 cells. N1E-115 cell membranes possess three Bordetella pertussis toxin (PTX) substrates assigned to alpha-subunits (G alpha) of Go (a G protein of unknown function) and "Gi (a G protein inhibitory to adenylate cyclase)-like" proteins and one substrate of Vibrio cholerae toxin corresponding to an alpha-subunit of Gs (a G protein stimulatory to adenylate cyclase). In undifferentiated cells, only one form of Go alpha was found, having a pI of 5.8 Go alpha content increased by approximately twofold from the undifferentiated state to 96 h of cell differentiation. This is mainly due to the appearance of another Go alpha form having a pI of 5.55. Both Go alpha isoforms have similar sizes on sodium dodecyl sulfate-polyacrylamide gels, are recognized by polyclonal antibodies to bovine brain Go alpha, are ADP-ribosylated by PTX, and are covalently myristylated in whole N1E-115 cells. In addition, immunofluorescent staining of N1E-115 cells with Go alpha antibodies revealed that association of Go alpha with the plasma membrane appears to coincide with the expression of the most acidic isoform and morphological cell differentiation. In contrast, the levels of both Gi alpha and Gs alpha did not significantly change, whereas that of the common beta-subunit increased by approximately 30% over the same period. These results demonstrate specific regulation of the expression of Go alpha during neuronal differentiation.

Adenylate Cyclase Toxin↗
PubMed1990

Practical and economical method for using biotinylated DNA probes with bacterial colony blots to identify diarrhea-causing Escherichia coli.

A simple and economical method was developed for using biotinylated DNA probes to hybridize with bacterial colonies belonging to the various categories of diarrhea-causing Escherichia coli. Simplification and cost containment were achieved by using Whatman no. 541 filter papers instead of nitrocellulose, by minimizing the concentration of proteinase K (an expensive but necessary reagent used to pretreat the colony blots prior to hybridization with biotin-labeled DNA probes) and by reusing hybridization solution containing labeled probe DNA. After exposing the colony blots to lysing solution and steam, followed by lysozyme (1.5 mg/ml), sucrose (25%), and proteinase K (10 micrograms/ml) treatments, biotinylated probes were used to detect enterotoxigenic, enteropathogenic, enterohemorrhagic, diffuse adherence, and enteroinvasive categories of diarrhea-causing E. coli with a high level of sensitivity and specificity. Three independent observers who were experienced in reading DNA blots recorded remarkably similar results, while less satisfactory results were obtained when the blots were read by an inexperienced observer. This technique will be useful in laboratories in which radioactive isotopes are unavailable or impractical and in which budgets are restricted.

Biotin↗
PubMed1990

Cholecystokinin-induced formation of inositol phosphates in pancreatic acini.

For cholecystokinin (CCK) and the partial agonist CCK-JMV-180 [Boc-Nle28,31,CCK-(27-32)-2-phenylethyl ester], we examined their abilities to stimulate the accumulation of inositol phosphates (IP), mobilize intracellular calcium, and stimulate enzyme secretion in rat pancreatic acini. CCK-8 caused an increase in [3H]IP2 and [3H]IP3 at 10 s and a slower increase in [3H]IP1. High-pressure liquid chromatography separation demonstrated that at 10 s 100% of the increase of [3H]IP3 was IP3(1,4,5). CCK-JMV-180 caused no increase in [3H]IP3 at 10 s and only 28% of the maximal increase seen with CCK-8 at 15 min. CCK-8 caused an 11-fold increase in calcium outflux, whereas CCK-JMV-180 was only 45% as effective and 3,000 times less potent. CCK-JMV-180 antagonized the CCK-8-stimulated increase in [3H]IP3 and mobilization of intracellular calcium. CCK-8 caused an 81-fold increase at 2.5 s in IP3(1,4,5) measured by a mass radioreceptor assay and half-maximal stimulation occurred at 2 nM, whereas CCK-JMV-180 only caused a 3-fold increase. Analysis of the ability of CCK-8 or CCK-JMV-180 to stimulate enzyme secretion demonstrated that at low concentrations, each peptide stimulates enzyme secretion without causing detectable calcium mobilization, whereas at increasing peptide concentrations calcium mobilization occurs without detectable accumulation of IP3(1,4,5), but at still higher concentrations IP3(1,4,5) accumulation is finally detected. These results demonstrate that peptides that stimulate enzyme secretion by interacting with CCK receptors can cause maximal stimulation with minimal changes in calcium mobilization and maximal changes in calcium mobilization occur with minimal changes in IP3(1,4,5), suggesting marked amplification.

Amylases↗
PubMed1990

Cyclic cholecystokinin analogues that are highly selective for rat and guinea pig central cholecystokinin receptors.

Cholecystokinin (CCK) analogues (JMV310, JMV320, JMV328, and JMV332), obtained by side chain to side chain cyclization of a lysine residue in position 28 with a lysine residue in position 31, were found to be highly selective for the brain CCK receptor (CCK-B receptor), both in guinea pig and rat. In these analogues, the C-terminal tetrapeptide region of the molecule, which is the crucial determinant for binding to CCK-B receptors, has been constrained by cyclization. These analogues were highly potent in inhibiting binding of labeled CCK-8 to rat and guinea pig brain membranes (apparent affinity in the nanomolar range) but were poorly efficacious in inhibiting binding of labeled CCK-8 to rat or guinea pig pancreatic acini. In agreement with their low affinity for the pancreatic receptor, these CCK analogues were not very potent in stimulating amylase secretion. These cyclic CCK analogues were demonstrated to be highly selective for the brain CCK receptors.

Amylases↗
PubMed1989

Transglutaminase-mediated cross-linking of fibrinogen by human umbilical vein endothelial cells.

The interaction of endothelial cells with soluble or substrate-immobilized 125I-labeled fibrinogen (125I-FGN) was analyzed. Binding experiments involved incubation of 125I-FGN with cell suspensions at 4 degrees C. Bound ligand was quantitated by centrifugation of cells through silicone oil followed by scintillation analysis of the cell pellet. Calcium-dependent binding of 125I-FGN reached a maximum after 3 h and represented about 60% of the total. Half-maximal saturation occurred at 60 nM, and about 9 x 10(4) molecules were bound/cell at saturation (approximately 100 nM). Calcium-dependent binding was completely inhibited by unlabeled fibrinogen, partially inhibited by a monoclonal antibody (7E3) against glycoprotein IIb-IIIa, but not inhibited by fibrinogen fragments D or E, an anti-glycoprotein IIIa polyclonal antibody, or the Arg-Gly-Asp-Ser tetrapeptide. In contrast, the Arg-Gly-Asp-Ser tetrapeptide as well as the monoclonal antibody 7E3 markedly inhibited attachment of endothelial cells to substrate-immobilized fibrinogen, whereas fragment D or E did not. Both in suspension and monolayer, the 125I-FGN underwent cross-linking involving principally the A alpha chain. The transglutaminase inhibitors putrescine, histamine, and cystamine interfered with 125I-FGN binding and cross-linking by suspended cells. Since cross-linking in suspension was limited to bound 125I-FGN and since transglutaminase activity was not detectable in the binding buffer, cross-linking may have been mediated by a cell-associated transglutaminase.

Amino Acid Sequence↗
PubMed1989

Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide.

ACE (angiotensin-converting enzyme; peptidyl dipeptidase A; EC 3.4.15.1), cleaves C-terminal dipeptides from active peptides containing a free C-terminus. We investigated the hydrolysis of cholecystokinin-8 [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] and of various gastrin analogues by purified rabbit lung ACE. Although these peptides are amidated at their C-terminal end, they were metabolized by ACE to several peptide fragments. These fragments were analysed by h.p.l.c., isolated and identified by comparison with synthetic fragments, and by amino acid analysis. The initial and major site of hydrolysis was the penultimate peptide bond, which generated a major product, the C-terminal amidated dipeptide Asp-Phe-NH2. As a secondary cleavage, ACE subsequently released di- or tri-peptides from the C-terminal end of the remaining N-terminal fragments. The cleavage of CCK-8 and gastrin analogues was inhibited by ACE inhibitors (Captopril and EDTA), but not by other enzyme inhibitors (phosphoramidon, thiorphan, bestatin etc.). Hydrolysis of [Leu15]gastrin-(14-17)-peptide [Boc (t-butoxycarbonyl)-Trp-Leu-Asp-Phe-NH2] in the presence of ACE was found to be dependent on the chloride-ion concentration. Km values for the hydrolysis of CCK-8, [Leu15]gastrin-(11-17)-peptide and Boc-[Leu15]gastrin-(14-17)-peptide at an NaCl concentration of 300 mM were respectively 115, 420 and 3280 microM, and the catalytic constants were about 33, 115 and 885 min-1. The kcat/Km for the reactions at 37 degrees C was approx. 0.28 microM-1.min-1, which is approx. 35 times less than that reported for the cleavage of angiotensin I. These results suggest that ACE might be involved in the metabolism in vivo of CCK and gastrin short fragments.

Amino Acid Sequence↗
PubMed1989

Changes by two-dimensional echocardiography in the myocardial appearance of patients with end-stage renal disease.

A retrospective study of the clinical and biochemical data of all patients with end-stage renal disease who underwent 2-dimensional echocardiography at Tulane Medical Center between 1982 and 1986 was performed. Complete echocardiographic data were available for comparison in 53 patients. Highly reflective echoes were judged to be present in the myocardium of 81% of the patients. This characteristic is described as a "glistening speckled appearance." Patients with this characteristic had significantly greater left ventricular mass index (p = 0.0021).

Adult↗
PubMed1989

CCK-JMV-180: a peptide that distinguishes high-affinity cholecystokinin receptors from low-affinity cholecystokinin receptors.

When pancreatic acini are incubated with increasing concentrations of cholecystokinin octapeptide (CCK-8) the dose-response curve for stimulation of enzyme secretion increases, reaches a maximum and then decreases. The upstroke of the dose-response curve reflects occupation of high-affinity, stimulatory CCK receptors (Kd 69 pM), whereas the downstroke of the dose-response curve reflects occupation of low-affinity inhibitory CCK receptors (Kd 10 nM). In the present study, we used dispersed acini from rat pancreas to examine the effects of CCK-JMV-180, an analogue of the C-terminal heptapeptide of CCK (CCK-7) having the structure BOC-Tyr(SO3) Ahx-Gly-Trp-Ahx-Asp2 phenylethyl ester. CCK-JMV-180 inhibited binding of 125I-labelled CCK-8 to pancreatic acini. Computer analysis of the dose-inhibition curve indicated that CCK-JMV-180 interacted with both classes of CCK receptor and had a Kd of 2.2 nM for high-affinity CCK receptors and a Kd of 19 nM for low-affinity CCK receptors. Occupation of high-affinity CCK receptors by CCK-JMV-180 caused a 14-fold increase in amylase secretion, the same increase caused by occupation of these high-affinity receptors by CCK-7 or CCK-8. Occupation of low-affinity CCK receptors by CCK-JMV-180 did not alter amylase secretion, in contrast to occupation of these low-affinity receptors by CCK-7 or CCK-8, each of which caused inhibition of amylase secretion. Furthermore, occupation of the low-affinity CCK receptors by CCK-JMV-180 reversed the inhibition of amylase secretion caused by a supramaximal concentration of CCK-8. The present results indicate that CCK-JMV-180 interacts with high-affinity CCK receptors and with low-affinity CCK receptors, and has a functionally distinct action at each class of receptor: CCK-JMV-180 is an agonist at the high-affinity receptors and a competitive antagonist at the low-affinity receptors.

Amylases↗
PubMed1989

The alien hand syndrome. Clinical and postmortem findings.

Two patients had automatonlike movements of their left hands and arms (alien hand syndrome) following damage to the brain. Autopsy findings in one patient demonstrated gunshot wound damage to the medial frontal white matter bilaterally, as well as the corpus callosum, right basal ganglia, internal capsule, and thalamus. The other patient had a ruptured anterior communicating aneurysm, with subsequent resection of the right frontal gyrus rectus. We postulate that this syndrome is due to the combination of a partial callosectomy and mesial frontal lesions.

Adult↗
PubMed1989

Subcellular localization of a cysteine proteinase from Trypanosoma cruzi.

Epimastigotes of Trypanosoma cruzi, Tulahuén strain, Tul 2 stock, contain a cysteine proteinase able to degrade azocasein at pH 5. This enzyme activity was extracted from whole cells by digitonin concentrations higher than those required for cytosolic markers, lower than those required for glycosomal and mitochondrial markers, and very similar to those required for solubilization of the acidic alpha-mannosidase. Both, the azocasein-degrading proteinase and the alpha-mannosidase, showed similar latency and distribution in subcellular fractions (the large granule fraction was the most active), and the same behavior in isopycnic sucrose gradient centrifugation; a broad peak centered at an equilibrium density of about 1.15 g cm-3, with a shoulder between 1.07 and 1.10 g cm-3, was obtained for both enzymes. The results suggest that the cysteine proteinase activity is placed in the lysosomes.

Animals↗
PubMed1989

Dose related efficacy of adenosine triphosphate in spontaneous supraventricular tachyarrhythmias.

Intravenous adenosine triphosphate has been proved to be useful for the treatment of supraventricular tachyarrhythmias. The optimal dose to be employed, however, has yet to be stated. Forty-two episodes of spontaneous paroxysmal supraventricular tachycardia, observed in 33 patients (16 men and 17 women, mean age 51 years) were treated with intravenous boluses. These were given in 10 mg increments at increasing doses from 10 to 50 mg at intervals of three minutes if the arrhythmia persisted despite the previous dose. When using a dose less than or equal to 40 mg, tachycardia was terminated in 37 of 42 episodes in less than 50 seconds. In four of the remaining five, atrial flutter and ectopic atrial tachycardia were diagnosed after administration of adenosine triphosphate. The other patient was subsequently found to have an atrioventricular reentrant tachycardia incorporating two accessory pathways. More than half of the treated episodes of supraventricular tachycardia terminated with the minimal dose of 10 mg and 7.1% required 40 mg. In five patients, arrhythmia ceased and reappeared despite the use of adenosine triphosphate. All the patients experienced an unpleasant feeling of dyspnoea or suffocation after injection of the drug. Sinus pauses and bradycardia following termination of the arrhythmia were directly correlated with the dose employed (P less than 0.05). We conclude that adenosine triphosphate is a useful, safe and effective drug at low dose in correctly diagnosed reentrant tachycardias involving the atrioventricular node. It is also useful as a diagnostic tool in patients with supraventricular tachyarrhythmias.

Adenosine Triphosphate↗