Release of avian neurotensin in response to intraluminal contents in the duodenum of chickens.

Peripheral and hepatic-portal plasma levels of neurotensin (NT) in fed and fasted chickens were determined using RIA. Portal levels of NT(1-13) (fed = 61.3 ± 3.

Enhanced vascular permeability is hypothesized to promote inflammation-induced carcinogenesis and tumor development via extravasation of large molecular proteins into the tissue.

We propose that the growth of solid tumors is dependent, in part, on the entry of large molecular blood-borne growth regulators into the tissue and is facilitated by the highly permeable nature of tumor blood vessels. There is abundant evidence that the tumor vasculature is hyperpermeable and tumor growth is dependent on mediators that increase vascular permeability (e.g.

Zinc pyrithione induces ERK- and PKC-dependent necrosis distinct from TPEN-induced apoptosis in prostate cancer cells.

Zinc dyshomeostasis can induce cell death. However, the mechanisms involved have not been fully elucidated in prostate cancer (PCa) cells, which differ dramatically from normal cells in their zinc handling ability. Here, we studied the effects of the ionophore Zn-pyrithione (ZP) and the chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN).

HMC-1 human mast cells synthesize neurotensin (NT) precursor, secrete bioactive NT-like peptide(s) and express NT receptor NTS1.

Objective And Design: To determine if mast cells synthesize the inflammatory peptide, neurotensin (NT), secrete immunoreactive and bioactive NT, and express the NT receptor NTS1.

Materials: HMC-1 cells, pleural mast cells from Sprague-Dawley rats, LAD2 mast cells, and human cord blood mast cells were used.

Treatment: HMC-1 cells were stimulated with NT, C48/80, mastoparan, or PGE(2).

Protein kinase C inhibitors alter neurotensin receptor binding and function in prostate cancer PC3 cells.

Prostate cancer PC3 cells expressed constitutive protein kinase C (PKC) activity that under basal conditions suppressed neurotensin (NT) receptor function. The endogenous PKC activity, assessed using a cell-based PKC substrate phosphorylation assay, was diminished by PKC inhibitors and enhanced by phorbol myristic acid (PMA). Accordingly, PKC inhibitors (staurosporine, Go-6976, Go-6983, Ro-318220, BIS-1, chelerythrine, rottlerin, quercetin) enhanced NT receptor binding and NT-induced inositol phosphate (IP) formation.

Neurotensin receptor binding and neurotensin-induced growth signaling in prostate cancer PC3 cells are sensitive to metabolic stress.

Neurotensin (NT) stimulates the proliferation of prostate cancer PC3 cells, which express high levels of its G protein-coupled receptor NTS1. To shed light on mechanisms that might serve to coordinate mitogenic responses to metabolic status, we studied the effects of metabolic inhibitors on NTS1 function. We also related these effects to cellular ATP levels and to the activation of AMP-activated protein kinase (AMPK).

Involvement of neurotensin in cancer growth: evidence, mechanisms and development of diagnostic tools.

Focusing on the literature of the past 15 years, we evaluate the evidence that neurotensin and neurotensin receptors participate in cancer growth and we describe possible mechanisms. In addition, we review the progress achieved in the use of neurotensin analogs to image tumors in animals and humans. These exciting advances encourage us to pursue further research and stimulate us to consider novel ideas regarding the multiple inputs to cancer growth that neurotensin might influence.

Inhibition of progenitor dendritic cell maturation by plasma from patients with peripartum cardiomyopathy: role in pregnancy-associated heart disease.

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder.

Regulation of neurotensin receptor function by the arachidonic acid-lipoxygenase pathway in prostate cancer PC3 cells.

Neurotensin (NT) elevates leukotriene levels in animals and stimulates 5-HETE formation in prostate cancer PC3 cells. PC3 cell growth is stimulated by NT and inhibited by lipoxygenase (LOX) blockers. This led us to test LOX blockers (NDGA, MK886, ETYA, Rev5901, AA861 and others) for effects on NT binding and signaling.

Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution.

Objective: To determine the incidence and prognosis of peripartum cardiomyopathy (PPCM) in rural Haiti.

Patients And Methods: Prospectively identified patients with PPCM treated at the Hospital Albert Schweitzer (HAS), Deschapelles, Haiti, were included in this study. Patients who presented to HAS from February 1, 2000, to January 31, 2005, were identified through a search of the HAS PPCM Registry.

Involvement of arachidonic acid metabolism and EGF receptor in neurotensin-induced prostate cancer PC3 cell growth.

Dietary fats, which increase the risk of prostate cancer, stimulate release of intestinal neurotensin (NT), a growth-promoting peptide that enhances the formation of arachidonic acid metabolites in animal blood. This led us to use PC3 cells to examine the involvement of lipoxygenase (LOX) and cyclooxygenase (COX) in the growth effects of NT, including activation of EGF receptor (EGFR) and downstream kinases (ERK, AKT), and stimulation of DNA synthesis. NT and EGF enhanced [3H]-AA release, which was diminished by inhibitors of PLA2 (quinacrine), EGFR (AG1478) and MEK (U0126).

Insulin-like growth factor (IGF) induced proliferation of human lung fibroblasts is enhanced by neurotensin.

Fibroblasts are key cells in tissue repair and important contributors to the inflammatory response. Insulin-like growth factors (IGFs) have been shown to participate in growth, in immune responses and in tissue repair where they stimulate cell growth. Neurotensin (NT) has been suggested to participate in inflammation and in tissue repair and is an autocrine or paracrine growth factor for several cancer cell types.

Impact of pregnancy-related heart failure on humoral immunity: clinical relevance of G3-subclass immunoglobulins in peripartum cardiomyopathy.

Background: The impact and clinical relevance of pregnancy-related heart failure (HF) on humoral immunity are not known. Heart failure is often characterized by immunoglobulins (Ig) that differ in subclass profile with etiology. Subclass immunoglobulins differ in the biologic information they confer in disease.

Neurotensin activates GABAergic interneurons in the prefrontal cortex.

Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons.

The effect of neurotensin on insulin-induced proliferation of human fibroblasts.

Neurotensin has been shown to influence growth in a number of cancerous and non-cancerous cells and to enhance the proliferative effects of growth factors without itself inducing proliferation. Here we show that neurotensin potentiates the proliferative effects of insulin on IMR90 human fibroblasts in a concentration and neurotensin receptor type 1-dependent manner. This potentiating effect of neurotensin was blocked by inhibitors of phospholipase C and protein kinase C, was accompanied by an increase in the level of soluble inositol phosphates and did not involve an autocrine factor.

Involvement of MAP-kinase, PI3-kinase and EGF-receptor in the stimulatory effect of Neurotensin on DNA synthesis in PC3 cells.

The mechanism by which neurotensin (NT) promotes the growth of prostate cancer epithelial cells is not yet defined. Here, androgen-independent PC3 cells, which express high levels of the type 1 NT-receptor (NTR1), are used to examine the involvement of epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (ERK, SAPK/JNK and p38), PI3 kinase and PKC in the mitogenic effect of NT. NT dose dependently (0.

The relationship between the esophageal tissue content of neurotensin and the presence or absence of esophageal inflammation.

Neurotensin (NT) decreases lower esophageal sphincter pressure and impedes gastric emptying, thus exacerbating gastroesophageal reflux. The aim was to determine the content of esophageal tissue NT in patients with erosive esophagitis compared to those with normal endoscopy with or without abnormal acid exposure. Consecutive patients (N = 21) with gastroesophageal reflux disease symptoms underwent an upper endoscopy, at which two biopsies from opposite walls were obtained from normal-appearing mucosa.

Polyphenolic antioxidants mimic the effects of 1,4-dihydropyridines on neurotensin receptor function in PC3 cells.

This study aimed to determine the mechanism(s) by which 1,4-dihydropyridine Ca2+ channel blockers (DHPs) enhance the binding of neurotensin (NT) to prostate cancer PC3 cells and inhibit NT-induced inositol phosphate formation. Earlier work indicated that these effects, which involved the G protein-coupled NT receptor NTR1, were indirect and required cellular metabolism or architecture. At the micromolar concentrations used, DHPs can block voltage-sensitive and store-operated Ca2+ channels, K+ channels, and Na+ channels, and can inhibit lipid peroxidation.

Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats.

Neurotensin (NT), a hormone released from intestine by ingested fat, facilitates lipid digestion by stimulating pancreatic secretion and slowing the movement of chyme. In addition, NT can contract the gall bladder and enhance the enterohepatic circulation (EHC) of bile acids to promote micelle formation. Our recent finding that NT enhanced and an NT antagonist inhibited [(3)H]taurocholate ([(3)H]TC) absorption from proximal rat small intestine indicated a role for endogenous NT in the regulation of EHC.

Ca2+ channel blockers enhance neurotensin (NT) binding and inhibit NT-induced inositol phosphate formation in prostate cancer PC3 cells.

Neurotensin (NT) stimulates Ca2+ release and Ca2+ influx in many cells. Its contractile effects in smooth muscle are inhibited by removal of Ca2+ and by Ca2+ channel blockers (CCBs). To better understand NT signaling in prostate cancer PC3 cells, blockers of voltage-gated and store-operated Ca2+ channels (VGCC and SOCC) were tested for effects on NT-binding and signaling.

Is peripartum cardiomyopathy an organ-specific autoimmune disease?

Peripartum cardiomyopathy (PPCM) is a rare and serious heart disease that exclusively afflicts women during childbearing years. Symptoms include rapid onset of cardiovascular insufficiency occurring during pregnancy, initiated anytime between the third trimester until 5 months post-partum in the absence of any other signs or history of heart disease. The rare incidence of PPCM and the absence of any relevant animal models have limited research and understanding of the pathogenic mechanisms involved.

Histamine releasing peptide (HRP) has proinflammatory effects and is present at sites of inflammation.

Albumin, the most abundant plasma protein, readily enters sites of inflammation during the period of increased vascular permeability. There it encounters proteases released from mast cells and invading leukocytes which earlier work has shown can act on albumin to liberate the peptide, histamine releasing peptide (HRP), first identified and named by its ability to stimulate histamine release from isolated mast cells. In this report we show that HRP releases histamine from cutaneous mast cells in vivo resulting in increased vascular permeability and persistent edema while in vitro, HRP promotes chemotaxis of leukocytes and enhances macrophage phagocytosis.

Autoimmune mechanisms as the basis for human peripartum cardiomyopathy.

The etiology and mechanisms of pathogenesis of human peripartum cardiomyopathy (PPCM) remain unknown. The incidence and prevalence of this disease is rare in some parts of the world and more common in others. The purpose of this review is to summarize our current knowledge of the factors that have been entertained which may contribute to the pathogenesis of PPCM with special emphasis on more recent data from our laboratory that provide support to the view that this disease is an autoimmune disease with multiple contributing factors and effector mechanisms.

Myocardial preconditioning factors evoke mesenteric ischemic tolerance via opioid receptors and K(ATP) channels.

We have shown that a reverse-phase concentrate generated from the effluent of preconditioned (PC) rabbit hearts evokes a cardioprotective effect in virgin acceptor hearts. With the use of a model of sustained (1 h) simulated ischemia in isolated, spontaneously contracting rabbit jejunum, our current aims were to 1) determine whether protective factor(s) released from PC hearts can improve ischemic tolerance in noncardiac tissue; and 2) obtain preliminary insight into the mediator(s) involved in triggering and eliciting this remote protection. Recovery of contractile force following reoxygenation (our index of ischemic tolerance) was enhanced in jejunal segments pretreated with concentrate generated from PC hearts (33 +/- 3% of baseline, P < 0.

Delta opiates increase ischemic tolerance in isolated rabbit jejunum.

Unlabelled: Mammalian hibernation is mediated by humoral agonists of the delta opioid receptor (DOR). Moreover, transfer of either humoral or synthetic DOR agonists to non-hibernators reportedly induces a state of improved myocardial ischemic tolerance.

Objective: To determine whether the DOR agonist D-Ala 2, D-Leu 5, enkephalin (DADLE) similarly elicits protection in noncardiac-i.