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E Baldi

Publications and source records attributed to E Baldi.

At least 91 records · Page 5Linked to original sources
PubMed1992

Endothelin stimulates phosphatidic acid formation in cultured rat mesangial cells: role of a protein kinase C-regulated phospholipase D.

We have previously reported that endothelin-1 stimulates phospholipase C-induced hydrolysis of phosphatidylinositol-4,5-bisphosphate. Other signal transduction pathways that hydrolyze alternative phospholipids through phospholipase D may also mediate endothelin-stimulated cellular responses. We initially evaluated endothelin-dependent generation of 32P-phosphatidic acid as an indirect indication of phospholipase D activity in rat mesangial cells. Endothelin (10(-7) M) induced an elevation of phosphatidic acid that was maximal at 15 min and persisted upward of 60 min. Pretreatment with the diacylglycerol-kinase inhibitor, R59022, did not reduce formation of endothelin-stimulated 32P-phosphatidic acid, demonstrating that the sequential actions of phospholipase C/diacylglycerol kinase do not contribute to endothelin-stimulated phosphatidic acid formation. We next conclusively identified a role for phospholipase D in the generation of phosphatidic acid by assessing the formation of 3H-phosphatidylethanol from 3H-alkyl lyso glycerophosphocholine and exogenous ethanol. Endothelin stimulated 3H-alkyl phosphatidylethanol formation in the presence but not the absence of 0.5% ethanol. Also, endothelin induced a concomitant elevation of 3H-alkyl-phosphatidic acid that was significantly reduced when the cells were exposed to exogenous ethanol, reflecting the formation of phosphatidylethanol. In addition, endothelin stimulated the release of 3H-choline and 3H-ethanolamine, demonstrating that additional phospholipids may serve as substrates for phospholipase D. Phorbol esters and synthetic diglycerides mimicked the effects of endothelin to stimulate phospholipase D and inhibitors of protein kinase C significantly reduced endothelin-stimulated phospholipase D. In addition, endothelin did not stimulate phosphatidylethanol formation in protein kinase C down-regulated cells. The calcium ionophore, ionomycin, did not stimulate phospholipase D and mesangial cells pretreated with BAPTA to chelate cytosolic calcium did not show a diminished endothelin-stimulated phospholipase D. Thus these data demonstrate that mesangial cells possess a protein kinase C-regulated phospholipase D activity that can be stimulated with endothelin.

Animals↗
PubMed1992

Minaprine cancels scopolamine effects on the rat's acquisition of passive avoidance responses in two multitrial paradigms.

The antiamnesic activity of minaprine has been studied in male Wistar rats. Two multitrial paradigms were employed: the light-dark box test (aversive stimulus: 0.6-mA foot-shocks) and the tail-handling test (aversive stimulus: manual tail-handling). In both paradigms, intraperitoneal scopolamine administration 30 min before testing significantly impaired the acquisition of the passive avoidance conditioned response. There were no significant differences in either paradigm between control rats and those to whom scopolamine and minaprine were simultaneously administered. These results show that minaprine fully protects the acquisition process of conditioned responses against scopolamine impairment not only in one-trial tests but also in multitrial paradigms. The effects of minaprine in reversing memory deficits are discussed in relation to its stimulating activity on central cholinergic systems.

Amnesia↗
PubMed1992

Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients.

Liver perisinusoidal fat-storing cells (FSC) show morphological and ultrastructural characteristics similar to pericytes regulating local blood flow in other organs. In the present study we have analyzed whether FSC respond to local vasoconstrictors such as thrombin, angiotensin-II, and endothelin-1 with an increase in intracellular free calcium concentration ([Ca2+]i) coupled with effective cell contraction. All agonists tested induced a rapid and dose-dependent increase in [Ca2+]i followed by a sustained phase lasting several minutes in confluent monolayers of Fura-2-loaded human FSC. Pharmacological studies performed using different Ca2+ channel blockers indicated that, at least for thrombin and angiotensin-II, the sustained phase is due to the opening of voltage-sensitive membrane Ca2+ channels. To analyze the temporal and spatial dynamics of Ca2+ release in response to these agonists, we performed experiments on individual Fura-2-loaded human FSC using a dual wavelength, radiometric video imaging system. The rise in [Ca2+]i was exclusively localized to the cytoplasm, particularly in the branching processes. Increases in [Ca2+]i more than four-fold were associated with a simultaneous and transient reduction of cell area indicating reversible cell contraction. Our results indicate that the Ca(2+)-dependent contraction of human FSC in vitro may reflect a potential role in regulating sinusoidal blood flow in vivo.

Angiotensin II↗
PubMed1991

Respiratory syncytial virus infection of human mononuclear phagocytes stimulates synthesis of platelet-activating factor.

Production of platelet-activating factor 1-O-alkyl-2-acetyl-sn-glycero-3- phosphocholine (PAF), a potent mediator of inflammation, by mononuclear phagocytes varies with their stage of cellular differentiation and the nature of the eliciting stimulus. The human monocytic cell line U937 can be induced to differentiate to a macrophage-like cell following phorbol myristate acetate exposure, and after differentiation, these cells efficiently support replication of respiratory syncytial virus (RSV). U937 cells induced to differentiate with phorbol myristate acetate demonstrated a time-dependent decrease in PAF synthesis. RSV infection of these differentiated U937 cells caused a sustained stimulation of PAF synthesis that paralleled viral replication and was dependent on infectious virus. Virus increased the activity of lyso-PAF:acetyl-CoA acetyl-transferase (PAF acetyltransferase) in cell lysates, thus enhancing the anabolic pathway of PAF synthesis without altering the activity of PAF acetylhydrolase, which regulates PAF catabolism. RSV infection of human monocytes also caused a marked increase in [3H] monocytes also caused to uninfected monocytes. Thus, virus infection serves as a novel stimulus to induce PAF synthesis in human mononuclear phagocytes and suggests that increased PAF production may have a critical role in the inflammatory response to RSV.

Acetyltransferases↗
PubMed1991

Effects of nucleus basolateralis amygdalae neurotoxic lesions on some spontaneous activities in the rat.

Drinking, feeding, locomotion and exploratory activity of male Wistar rats were assessed after bilateral stereotaxic administration of ibotenic acid in the nucleus basolateralis amygdalae. Feeding, drinking and locomotion were measured in an activity cage, while exploratory activity was determined in a multiple Y-maze. In the 24-hour cycle, lesioned animals exhibited unvaried feeding, decreased drinking and increased locomotion. Exploration was also increased. The results show that this nucleus is not involved in quantitative feeding control, while it does exert a significant facilitatory influence on drinking. It also exerts an inhibitory influence on exploration and on locomotion.

Amygdala↗
PubMed1991

Endothelin receptors and coupled GTP-binding proteins in glomerular mesangial cells.

Endothelins (ETs) are a family of vasoactive peptides with profound biological actions in diverse cell systems. Among its varied actions, ET stimulates phospholipase C (PLC) in cultured mesangial cells. We investigated the presence of specific ET receptors in rat mesangial cells in culture, and studied the role of GTP-binding proteins (G proteins) in coupling PLC to the endothelin receptor. [125I]ET binding was time- and temperature-dependent, and Scatchard analysis of saturation data showed a single class of high-affinity binding sites. Heterologous displacement with two related peptides, ET-3 and sarafotoxin (SFTX), revealed the presence of two binding sites for these isopeptides. Preincubation of cells with ET-1 reduced the receptor number without affecting Kd, and this effect was not prevented by protein kinase C inhibition or downregulation. We confirmed the presence of a 41- to 43-kDa pertussis toxin substrate in rat mesangial cell membranes in an ADP ribosylation assay. ET-1 inhibits and GDP beta S enhances toxin-catalyzed transfer of ADP-ribose to this substrate. ET-1 potentiated GTP gamma S-induced phosphatidylinositol (PI) hydrolysis in a concentration-dependent manner. In addition, pertussis toxin partially inhibited ET-stimulated PI hydrolysis in intact mesangial cells. Pertussis toxin also reduced the magnitude of ET-stimulated intracellular free calcium [( Ca2+ )i]. Thus, ET-1 binds to specific receptors on rat mesangial cells and activates PLC, in part, through a pertussis toxin-sensitive G-protein.

Adenosine Diphosphate Ribose↗
PubMed1991

Effects of endothelin on cultured human and rat glomerular mesangial cells.

Figure 5 summarizes our results and the data in the literature with regard to both short-term signalling and long-term signalling induced by endothelin. Short-term signalling, which induces vasoconstriction, is undoubtedly mediated by multiple signals including increments of cytosolic calcium, stimulation of protein kinase C and alkalinization of the cytosol. Endothelin also activates negative feedback pathways including arachidonate release with the synthesis of vasorelaxant prostaglandins and potentiation, in a prostaglandin-dependent manner, of beta-adrenergic-stimulated adenylate cyclase. Long-term signalling is less well understood and may depend not only on phospholipase activation with subsequent changes of calcium and protein kinase C but also stimulation of other protein kinases which phosphorylate key intermediates. Endothelin stimulates the transient appearance of protooncogenes that might play a role in the induction of cellular proliferation.

Animals↗
PubMed1991

Endothelin binding and receptor down regulation in rat glomerular mesangial cells.

Endothelin (ET) exerts various biological actions in mesangial cells, including stimulation of proliferation, contraction and phospholipase C activation. We investigated the presence of specific ET receptors on cultured rat mesangial cells, incubating the cells in the presence of [125I]ET-1 both at 22 and 4 degrees C. ET binding was time- and temperature-dependent and achieved equilibrium at 2 hr at 22 degrees C and at 5 hr at 4 degrees C. Scatchard analyses of equilibrium saturation curves with [125I]ET-1 and homologous competition curves revealed the presence of a single class of high-affinity binding sites (Kd = 31.4 +/- 7.08 pM). Heterologous competition experiments with ET-3 and sarafotoxin, however, indicated the presence of two binding sites for ET-related peptides in mesangial cells with a Kd for ET-3 of 41.5 +/- 19.2 and of 374 +/- 38.5 nM. Nifedipine and arginine-vasopressin failed to compete for ET binding sites. Preincubation of the cells with 1 nM ET-1 caused a dramatic decrease in ET binding capacity (from 0.5-0.02 fmol/100,000 cells) without affecting the Kd for the receptors (38 pM). ET receptor down regulation was not prevented by protein kinase C inhibition with H-7 and sangiovamycin, or after down regulation of protein kinase C induced by 24-hr preincubation with phorbol myristate acetate. ET receptor down regulation also exerts functional effects, as we found a decrease in intracellular-free calcium response to ET-1 after long-term preincubation with the same agonist. Our results are consistent with the presence of two binding sites for ET in rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Rhinomyiasis. Considerations on a clinical case].

A case of rhinomyiasis in a young woman returning from Greece is reported. The Authors emphasize that rhinomyiasis is very unusual in a healthy subject and that symptoms are the same as in allergic rhinitis and conjunctivitis. The need is stressed for correct and thorough information concerning the risks attendant upon sojourn in countries with poor socio-economic level.

Adult↗
PubMed1990

Platelet activating factor receptor blockade ameliorates murine systemic lupus erythematosus.

Untreated 16-week-old MRL/MpJ-lpr/lpr (lpr) mice, when compared to congenic MRL/MpJ-+/+ (+/+) mice, are characterized by a systemic lupus erythematosus syndrome, including severe glomerulonephritis, proteinuria and reduction of renal function. We hypothesized that platelet activating factor (PAF), a potent chemotactic and proinflammatory phospholipid mediator synthesized and released by circulating cells, glomerular mesangial and renal medullary interstitial cells, may play a role in the development of renal injury in lupus mice. We assessed renal PAF synthesis in lpr as well as +/+ mice and the effect of treatment with a PAF receptor blocking agent. Treatment with the PAF receptor antagonist L659,989 for four weeks, starting at 12 weeks of age, significantly reduced acute glomerular infiltration and proliferation, and prevented chronic glomerular histological changes; proteinuria and serum creatinine levels were also significantly reduced in treated mice. Renal PAF production was increased in lpr when compared to +/+ mice, and treatment with L659,989 restored renal PAF synthesis to the control levels. Our results support the hypothesis that PAF can be one of the mediators of glomerular injury characteristic of murine lupus nephritis, and indicate the possible therapeutic utility of PAF receptor antagonists in immunologic renal diseases.

Animals↗
PubMed1989

Renal hemodynamic and natriuretic effects of human atrial natriuretic factor infusion in cirrhosis with ascites.

We investigated the effect of a continuous infusion (50 micrograms as an initial bolus followed by a maintenance infusion at a rate of 0.1 micrograms/min.kg body wt for 45 min) of synthetic human atrial natriuretic factor (hANF) on renal hemodynamics and the renin-angiotensin-aldosterone system in 15 cirrhotic patients with ascites. Basal hANF levels were higher in cirrhotic patients when compared with normal values. Human atrial natriuretic factor infusion induced a significant decrease in mean blood pressure (from 77.8 +/- 1.1 to 68.6 +/- 1.5 mmHg, p less than 0.001) and a significant increase in heart rate (from 76.4 +/- 2.7 to 89.8 +/- 2.4 beats/min, p less than 0.001) in the patients studied. A remarkable increase in natriuresis (i.e., greater than or equal to 200 muEq/min) was observed in 5 patients (responders), whereas the infusion did not modify sodium excretion (i.e., less than or equal to 20 muEq/min) in 6 patients (nonresponders) and induced an intermediate response in 4 patients. Human atrial natriuretic factor-induced natriuresis was related to changes in renal hemodynamics that occurred during hANF infusion. In responders, the extent of the natriuretic response paralleled the increase of effective renal plasma flow and glomerular filtration rate; in non-responders the absent natriuretic response was associated with an evident reduction of these parameters. The reduction of blood pressure was similar in responders and nonresponders, but in the latter group it was followed by a marked increase of plasma renin activity and heart rate. It is likely that in nonresponders the natriuretic effect of hANF was blunted by the hemodynamic and hormonal changes triggered by the concomitant hANF-induced hypotension. This probably occurs in the presence of a greater reduction of effective arterial blood volume, as suggested by the higher baseline levels of plasma renin activity and the inability to increase free water excretion after a water load observed in nonresponders.

Adult↗
PubMed1989

Calcitonin gene-related peptide in the rat kidney: occurrence, sensitivity to capsaicin, and stimulation of adenylate cyclase.

The occurrence, effects and sensitivity to capsaicin and stimulation of adenylate cyclase of calcitonin gene-related peptide (CGRP) in the rat kidney have been investigated. CGRP-like immunoreactivity was higher in the medulla than in the papilla and the cortex. Capsaicin pretreatment significantly reduced CGRP-like immunoreactivity in the medulla and papilla while a small reduction was found in the cortex. CGRP-immunoreactive nerve fibres were observed surrounding blood vessels and occasionally in the vicinity of renal tubules and between the collecting ducts in the papilla. Some CGRP-immunoreactive fibres were also seen in kidneys from capsaicin-pretreated rats. Infusion of capsaicin (1 microM) through the renal artery of isolated and perfused rat kidney increased the CGRP-like immunoreactivity outflow from the venous effluent. This effect exhibited desensitization at the second challenge with the drug. Infusion of either capsaicin (1 microM) or CGRP (1 microM) reduced the increase of perfusion pressure induced by norepinephrine in isolated perfused rat kidney. Plasma protein extravasation was studied in the various regions of the rat kidney following infusion of capsaicin. No significant change was observed in the medulla, papilla or cortex after capsaicin administration. Adenylate cyclase activity was studied in membrane preparations from cortex, medulla and papilla of rat kidney. Cortical and medullary adenylate cyclase was stimulated in a concentration-dependent manner by salmon calcitonin, rat calcitonin and rat CGRP. Salmon calcitonin in these two areas showed half-maximal effective concentration approximately 1000 times lower and maximal stimulation only slightly higher than those of rat calcitonin and rat CGRP. However, in the papilla, only rat CGRP was able to induce a 60% increase of enzyme activity (half-maximal effective concentration, 19 +/- 1.6 nM). It is concluded that CGRP contained in capsaicin-sensitive sensory nerve may exert a local function in discrete areas of the rat kidney.

Adenylyl Cyclases↗
PubMed1989

Regional differences of adenylate cyclase stimulation by calcitonin and calcitonin gene-related peptide in the human kidney.

Calcitonin (CT) gene-related peptide (CGRP)-like immunoreactivity was detected in both the cortex and medullo-papillary portion of human kidneys. The two forms of human CGRP as well as rat CGRP were capable of stimulating renal cortical adenylate cyclase activity in a concentration-related manner, with a half-maximally effective concentration (EC50) similar to that of human CT and approximately 100-1000 times higher than that of salmon CT. However, in the medullo-papillary portion, in which both salmon CT and human CT were inactive, the two forms of human and rat CGRP increased adenylate cyclase activity by 100%, with EC50 values ranging from 36 nmol/L to 1 mumol/L. In cortical membrane preparations the effect of CGRP was additive to that of salmon CT. We concluded that regional differences exist in the effect of CT and CGRP in human renal tissue and that in the medullo-papillary portion and possibly in the cortex, CGRP stimulates adenylate cyclase activity through a CT-independent mechanism.

Adenylyl Cyclases↗
PubMed1988

Presence of dopamine-dependent adenylate cyclase activity in human renal cortex.

The effects of dopamine (DA) and of two selective DA DA1 agonists (SKF 38393 and SKF 82526) on adenylate cyclase activity were studied with human kidney cortex membrane preparations. DA elicited a dose-related stimulation of adenylate cyclase activity with an EC50 of 60 microM. The selective DA DA1 antagonist SCH 23390 behaved as a competitive antagonist, shifting the dose-response curve to the right. The non-selective beta-adrenoceptor antagonist (-)-propranolol did not affect the EC50 of the dose-response curve to DA but attenuated the maximal stimulatory effect of DA at concentrations higher than 100 microM. (+)-Sulpiride inhibited DA-induced adenylate cyclase stimulation in a dose-dependent manner with an IC50 of 4.6 X 10(-8) M but (-)-sulpiride was without effect. Both SKF 38393 and SKF 82526 stimulated the adenylate cyclase activity of human kidney cortex; this effect was completely antagonized by SCH 23390. Our results, demonstrating the presence of DA-sensitive adenylate cyclase activity, strongly suggest the presence of a DA receptor of the DA1 subtype in human kidney cortex.

Adenylyl Cyclases↗
PubMed1988

Measurement of catecholamines, met-enkephalin, somatostatin and substance P-like immunoreactivities in 12 human pheochromocytomas.

The present study was designed to evaluate the simultaneous presence of epinephrine (E), norepinephrine (NE), met-enkephalin (ME)-, somatostatin (SRIF)- and substance P (SP)- like immunoreactivities (LI) in extracts of 12 pheochromocytomas obtained at the time of surgery from 10 patients. Moreover, catecholamines and ME-LI levels were measured in peripheral plasma of each patient. Each pheochromocytoma was characterized by a high variability of ME-LI, SRIF-LI, SP-LI, E and NE levels. The highest E concentrations were found in tumors from patients with Multiple Endocrine Adenomatosis (MEA) IIa syndrome, whereas in sporadic pheochromocytomas NE was the main catecholamine. Among the neuropeptides ME-LI showed the highest intratumoral concentration, and SP-LI the lowest. No correlations were found between intratumoral levels of catecholamines and any of the neuropeptides or between any of the different neuropeptides measured. Plasma catecholamine levels were not correlated with intratumoral catecholamine levels. Plasma ME-LI was higher than normal in only one patient. No correlation was observed between tumoral CA or peptide content and the clinical picture. Our study confirms that human pheochromocytoma cells can synthetize different neuropeptides. The variability of the clinical picture very likely depends on the biochemical and biological heterogeneity of this chromaffin tumor.

Adrenal Gland Neoplasms↗
PubMed1988

Regional differences in the motor response to capsaicin in the guinea-pig urinary bladder: relative role of pre- and postjunctional factors related to neuropeptide-containing sensory nerves.

Capsaicin induced a contraction of isolated strips from the guinea-pig urinary bladder which was more evident in the dome than in the neck and inhibited contractions induced by field stimulation, particularly in the neck. Both responses exhibited prompt desensitization and were tetrodotoxin-resistant, suggesting a specific action on transmitter release from sensory nerve terminals. Indeed, the contractile response in the dome was prevented by a substance P antagonist while the inhibitory response in the neck was prevented by immunoblockade with anticalcitonin gene-related peptide (CGRP) serum. Substance P produced a contraction of the guinea-pig bladder, being about 5 times more potent in the dome than in the neck, while CGRP inhibited the evoked contractions, being about 8 times more potent in the neck than in the dome. Further, the maximal effect of CGRP in the neck was almost double that in the dome. Substance P- and CGRP-like immunoreactivity were detected in both the dome and the neck with no regional differences for each peptide. CGRP-like immunoreactivity was 6.3 and 7.9 times higher than substance P-like immunoreactivity in the dome and the neck, respectively. Exposure to capsaicin evoked release of both substance P- and CGRP-like immunoreactivity from the dome and the neck. Peak CGRP-like immunoreactivity released by capsaicin was 12.3 and 8 times greater than substance P-like immunoreactivity in the dome and the neck, respectively. For each peptide, no difference was found in peak release in the dome vs neck. Total substance P-like immunoreactivity released from the neck was 25% lower than that released from the dome. The ability of CGRP to stimulate accumulation of 3',5' cyclic adenosine monophosphate in membranes prepared from the bladder muscle was greater in preparations from the neck than from the dome. These findings indicate that postjunctional mechanisms (type and number of receptors for sensory neuropeptides, coupling with second messengers) are a major determinant of the type of motor responses consequent of the release of sensory neuropeptides from capsaicin-sensitive nerves.

Animals↗
PubMed1988

Vasopressin and oxytocin receptors in vagina, myometrium, and oviduct of rabbits.

In view of the presence of distinct oxytocin (OT) and vasopressin (VP) receptors in the male genital tract (porcine) we have reexamined the receptors for OT and AVP in the classical OT target tissue, female genital tract (rabbit). Neurohypophysial hormone receptors have been investigated in vagina, myometrium, and oviduct using quantitative ligand binding, adenylate cyclase, and contractility studies. Our results clearly indicate the presence of distinct OT and V1 VP receptors in the myometrium, while only the latter was detected in vagina and oviduct. In myometrium, estrogen treatment increases the density of OT and AVP receptors, while progesterone administration inhibits the estrogen effect. At the time of spontaneous delivery a dramatic (17-fold) increase was observed for the OT sites, while the AVP sites were unchanged. AVP receptors in vagina were sensitive to sex steroid administration and were reduced during pregnancy and delivery. Isometric contractility studies suggest that not just OT, but AVP can stimulate uterine strips, an effect that is partially reversible by the V1 antagonist d(CH2)5TyrMeAVP. In vagina only AVP is effective in inducing contractions at nanomolar concentrations. These results suggest a role for AVP as well as OT in regulation of the motility of female genital tract.

Adenylyl Cyclases↗