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Scientific Reports Nov 2015Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could...
Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES contraction. We used the selective agonists, neuromedin B (NMB), gastrin-releasing peptide (GRP), and [D-Tyr(6),Apa-4Cl(11),Phe(13),Nle(14)]bombesin-(6-14) (DTACPN-BN), as well as receptor antagonists of bombesin receptor subtype 2 (BB2), and 3 (BB3) for ex vivo contraction studies. Atropine, nifedipine, tetrodotoxin, and ω-conotoxin GVIA were used to explore the agonist-induced LES contraction mechanism. Reverse transcription polymerase chain reaction and immunohistochemistry were applied to detect bombesin receptor expression. Our results indicate that GRP and DTACPN-BN, but not NMB, induced tonic contractions of the porcine LES in a dose-dependent manner, and the contractions were inhibited with selective BB2 and BB3 antagonists. The GRP-induced contraction is mainly caused by L-type Ca(2+) channel-mediated Ca(2+) influx. However, DTACPN-BN-induced contractions are associated with neuronal conduction. RT-PCR and immunohistochemistry revealed that BB2 and BB3 were expressed in the porcine LES. Bombesin-induced tonic contraction of the LES is mediated through BB2 and BB3. Bombesin, BB2, and BB3 agonists might have the potential to treat GERD.
Topics: Animals; Bombesin; Calcium; Calcium Channels, L-Type; Esophageal Sphincter, Lower; Gastrin-Releasing Peptide; Muscle Contraction; Neurokinin B; Receptors, Bombesin; Swine
PubMed: 26522854
DOI: 10.1038/srep15879 -
The Journal of Pharmacology and... Mar 2016Stress exacerbates symptoms of bladder dysfunction including overactive bladder and bladder pain syndrome, but the underlying mechanisms are unknown. Bombesin-like...
Stress exacerbates symptoms of bladder dysfunction including overactive bladder and bladder pain syndrome, but the underlying mechanisms are unknown. Bombesin-like peptides and bombesin receptor types 1 and 2 (BB1 and BB2, respectively) in the brain have been implicated in the mediation/integration of stress responses. In this study, we examined effects of centrally administered bombesin on micturition, focusing on their dependence on 1) the sympathoadrenomedullary system (a representative mechanism activated by stress exposure) and 2) brain BB receptors in urethane-anesthetized (1.0-1.2 g/kg, i.p.) male rats. Intracerebroventricularly administered bombesin significantly shortened intercontraction intervals (ICI) at both doses (0.1 and 1 nmol/animal) without affecting maximal voiding pressure. Bombesin at 1 nmol induced significant increments of plasma noradrenaline and adrenaline levels, which were both abolished by acute bilateral adrenalectomy. On the other hand, adrenalectomy showed no effects on the bombesin-induced shortening of ICI. Much lower doses of bombesin (0.01 and 0.03 nmol/animal, i.c.v.) dose-dependently shortened ICI. Pretreatment with either a BB1 receptor antagonist (BIM-23127; d-Nal-cyclo[Cys-Tyr-d-Trp-Orn-Val-Cys]-Nal-NH2; 3 nmol/animal, i.c.v.) or a BB2 receptor antagonist (BEA; H-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; 3 nmol/animal, i.c.v.), respectively, suppressed the BB (0.03 nmol/animal, i.c.v.)-induced shortening of ICI, whereas each antagonist by itself (1 and 3 nmol/animal, i.c.v.) had no significant effects on ICI. Bombesin (0.03 nmol/animal, i.c.v.) significantly reduced voided volume per micturition and bladder capacity without affecting postvoid residual volume or voiding efficiency. These results suggest that brain bombesin and BB receptors are involved in facilitation of the rat micturition reflex to induce bladder overactivity, which is independent of the sympathoadrenomedullary outflow modulation.
Topics: Animals; Bombesin; Brain; Dose-Response Relationship, Drug; Injections, Intraventricular; Male; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Bombesin; Urination
PubMed: 26729307
DOI: 10.1124/jpet.115.230334 -
The Journal of Physiology Sep 20011. HCO3- secretion was investigated in interlobular duct segments isolated from guinea-pig pancreas using a semi-quantitative fluorometric method. Secretagogue-induced...
1. HCO3- secretion was investigated in interlobular duct segments isolated from guinea-pig pancreas using a semi-quantitative fluorometric method. Secretagogue-induced decreases in intracellular pH, following blockade of basolateral HCO3- uptake with a combination of amiloride and DIDS, were measured using the pH-sensitive fluoroprobe BCECF. Apparent secretory HCO3- fluxes were calculated from the initial rate of intracellular acidification. 2. In the presence of HCO3-, stimulation with secretin (10 nM) or forskolin (5 microM) more than doubled the rate of intracellular acidification. This effect was abolished in the absence of HCO3-. It was also abolished in the presence of HCO3- when DIDS and NPPB were applied to the luminal membrane by microperfusion. We therefore conclude that the increase in acidification rate is a useful index of secretagogue-induced HCO3- secretion across the luminal membrane. 3. Secretin, cholecystokinin (CCK) and bombesin each stimulated HCO3- secretion in a dose-dependent fashion. They evoked comparable maximal responses at about 10 nM and the EC50 values were 0.5 nM for secretin, 0.2 nM for CCK and 30 pM for bombesin. Acetylcholine (ACh) was also effective, with a maximum effect at 10 microM. 4. The stimulatory effect of CCK was blocked completely by the CCK1 receptor antagonist devazepide but not by the CCK2 receptor antagonist L365,260. The CCK analogue JMV-180 (Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-phenylethyl ester), which is an agonist of the high-affinity CCK1 receptor but an antagonist of the low-affinity receptor, also stimulated HCO3- secretion but with a smaller maximal effect than CCK. JMV-180 partially inhibited the response to a high concentration of CCK but not to a lower concentration, suggesting that both high- and low-affinity states of the CCK1 receptor evoke HCO3- secretion. 5. The stimulatory effect of bombesin was blocked completely by the gastrin-releasing peptide (GRP) receptor antagonist D-Phe6-bombesin(6-13)-methyl ester (BME) but not by the neuromedin B (NMB) receptor antagonist D-Nal-cyclo[Cys-Tyr-D-Trp-Orn-Val-Cys]-Nal-NH2 (BIM-23127). 6. Secretagogue-evoked fluid secretion was also examined using video microscopy to measure the rate of swelling of ducts whose ends had sealed during overnight culture. Secretin, CCK, bombesin and ACh all evoked fluid secretion with maximal rates of approximately 0.6 nl x min(-1) x mm(-2), and with concentration dependences similar to those obtained for HCO3- secretion. 7. We conclude that CCK, bombesin and ACh stimulate the secretion of a HCO3--rich fluid by direct actions on the interlobular ducts of the guinea-pig pancreas and that these responses are mediated by CCK1 receptors, GRP receptors and muscarinic cholinoceptors, respectively.
Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acetylcholine; Algorithms; Amiloride; Animals; Bicarbonates; Bombesin; Cell Membrane; Cholecystokinin; Diuretics; Guinea Pigs; In Vitro Techniques; Male; Microscopy, Video; Pancreatic Ducts; Perfusion; Secretin; Stimulation, Chemical
PubMed: 11559776
DOI: 10.1111/j.1469-7793.2001.00795.x -
Annals of Surgery Mar 1989Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several... (Review)
Review
Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several disease states such as diabetes, hypertension, cardiac disease and restrictive lung disease. When effective medical treatment of obesity becomes available, it will depend in part upon understanding the physiologic factors that control satiety. This review summarizes the information available on brain and gut control mechanisms of satiety. Brain nuclei located in the lateral hypothalamus, ventromedial hypothalamus, and other paraventricular areas are the sites of action for potent neuropeptides, such as cholecystokinin (CCK) and neuropeptide Y, that appear to regulate feeding. Exogenous CCK has been used clinically to decrease meal size in obese patients. The sites of the satiety cascade that are most often manipulated are the gastric and intestinal phases. Physiologic gastric distension is a potent inhibitor of feeding, whereas the intermeal interval may be regulated by intestinal signals released by food in the gut. Jejunal-ileal bypass has fallen from favor and has been replaced by gastric restrictive procedures that create a small proximal gastric pouch that empties into the small bowel (gastric bypass) or the distal stomach (gastroplasty). These operations rely partially on their ability to produce gastric distension in the proximal gastric pouch at an early stage during a meal. Thus, failure results if the pouch compensates by distending or if the stoma widens with subsequent loss of slow emptying. Improved medical and surgical treatment will be designed to intervene at specific sites of the satiety cascade as knowledge of the physiologic control mechanisms of satiety increases.
Topics: Bombesin; Cholecystokinin; Humans; Hypothalamus; Neuropeptide Y; Obesity, Morbid; Pancreatic Polypeptide; Satiation; Stomach
PubMed: 2647049
DOI: 10.1097/00000658-198903000-00001 -
Journal of Nuclear Medicine : Official... Mar 2022The gastrin-releasing peptide receptor (GRPR) is overexpressed in many solid malignancies, particularly in prostate and breast cancers, among others. We synthesized...
The gastrin-releasing peptide receptor (GRPR) is overexpressed in many solid malignancies, particularly in prostate and breast cancers, among others. We synthesized ProBOMB2, a novel bombesin derivative radiolabeled with Ga and Lu, and evaluated its ability to target GRPR in a preclinical model of human prostate cancer. ProBOMB2 was synthesized in solid phase using fluorenylmethoxycarbonyl chemistry. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was coupled to the terminus and separated from the GRPR-targeting sequence by a cationic 4-amino-(1-carboxymethyl)-piperidine spacer. Binding affinity for both human and murine GRPR was determined using a cell-based competition assay, whereas a calcium efflux assay was used to measure the agonist and antagonist properties of the derivatives. ProBOMB2 was radiolabeled with Lu and Ga. SPECT and PET imaging and biodistribution studies were conducted using male immunocompromised mice bearing GRPR-positive PC-3 human prostate cancer xenografts. Ga-ProBOMB2 and Lu-ProBOMB2 bound to PC-3 cells with an inhibition constant of 4.58 ± 0.67 and 7.29 ± 1.73 nM, respectively. Ga-ProBOMB2 and Lu-ProBOMB2 were radiolabeled with a radiochemical purity greater than 95%. Both radiotracers were excreted primarily via the renal pathway. PET images of PC-3 tumor xenografts were visualized with excellent contrast at 1 and 2 h after injection with Ga-ProBOMB2, and there was very low off-target organ accumulation. Lu-ProBOMB2 enabled clear visualization of PC-3 tumor xenografts by SPECT imaging at 1, 4, and 24 h after injection Lu-ProBOMB2 displayed higher tumor uptake than Ga-ProBOMB2 at 1 h after injection. Lu-ProBOMB2 tumor uptake at 1, 4, and 24 h after injection was 14.9 ± 3.1, 4.8 ± 2.1, and 1.7 ± 0.3 percentage injected dose per gram of tissue, respectively. Ga-ProBOMB2 and Lu-ProBOMB2 are promising radiotracers with limited pancreas uptake, good tumor uptake, and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.
Topics: Animals; Bombesin; Cell Line, Tumor; Gallium Radioisotopes; Humans; Male; Mice; Molecular Imaging; Prostatic Neoplasms; Receptors, Bombesin; Tissue Distribution
PubMed: 34301778
DOI: 10.2967/jnumed.120.257758 -
Journal of Nuclear Medicine : Official... Sep 2013Receptor-targeted agents, such as gastrin-releasing peptide receptor (BB2r)-targeted peptides, have been investigated extensively in preclinical and clinical studies. In...
UNLABELLED
Receptor-targeted agents, such as gastrin-releasing peptide receptor (BB2r)-targeted peptides, have been investigated extensively in preclinical and clinical studies. In an attempt to increase the effectiveness of diagnostic or radiotherapeutic agents, we have begun to explore the incorporation of the hypoxia-selective prodrug 2-nitroimidazole into receptor-targeted peptides. Hypoxia is a well-known characteristic of many solid tumors, including breast, prostate, and pancreatic cancers. The aim of this approach is to use the hypoxia-trapping capability of 2-nitroimidazoles to increase the retention of the agent in hypoxic, BB2r-positive tumors. We have demonstrated that incorporation of one or more 2-nitroimidazoles into the BB2r-targeted peptide significantly increases the in vitro retention of the agent in hypoxic prostate cancer cells. The study described herein represents our first investigation of the in vivo properties of these hypoxia-enhanced BB2r-targeted agents in a PC-3 xenograft mouse model.
METHODS
Four (111)In-labeled BB2r-targeted conjugates--(111) IN-1, (111) IN-2, (111) IN-3, and (111) IN-4, composed of 2-nitroimidazole moieties of 0, 1, 2, and 3, respectively--were synthesized, labeled, and purified. The BB2r binding affinities, externalization, and protein-association properties of these radioconjugates were assessed using the BB2r-positive PC-3 human prostate cancer cell line under hypoxic and normoxic environments. The in vivo biodistribution and micro-SPECT/CT imaging of the (111) IN-1, (111) IN-2, and (111) IN-4 radioconjugates were investigated in PC-3 tumor-bearing severely combined immunodeficient mice.
RESULTS
All conjugates and (nat)In-conjugates demonstrated nanomolar binding affinities. (111) IN-1, (111) IN-2, (111) IN-3, and (111) IN-4 demonstrated 41.4%, 60.7%, 69.1%, and 69.4% retention, correspondingly, of internalized radioactivity under hypoxic conditions relative to 34.8%, 35.3%, 33.2%, and 29.7% retention, respectively, under normoxic conditions. Protein-association studies showed significantly higher levels of association under hypoxic conditions for 2-nitroimidazole-containing BB2r-targeted radioconjugates than for controls. On the basis of the initial 1-h uptake in the PC-3 tumors, (111) IN-1, (111) IN-2, and (111) IN-4 demonstrated tumor retentions of 1.5%, 6.7%, and 21.0%, respectively, by 72 h after injection. Micro-SPECT/CT imaging studies of (111) IN-1, (111) IN-2, and (111) IN-4 radioconjugates resulted in clear delineation of the tumors.
CONCLUSION
On the basis of the in vitro and in vivo studies, the BB2r-targeted agents that incorporated 2-nitroimidazole moieties demonstrated improved retention. These results indicate that further exploration into the potential of hypoxia-selective trapping agents for BB2r-targeted agents, as well as other targeted compounds, is warranted.
Topics: Animals; Bombesin; Cell Hypoxia; Cell Line, Tumor; Indium Radioisotopes; Isotope Labeling; Male; Metabolic Clearance Rate; Mice; Mice, SCID; Organ Specificity; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Bombesin; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution
PubMed: 23896558
DOI: 10.2967/jnumed.112.117986 -
The Journal of Neuroscience : the... Jul 2023Respiratory chemoreceptor activity encoding arterial Pco and Po is a critical determinant of ventilation. Currently, the relative importance of several putative...
Respiratory chemoreceptor activity encoding arterial Pco and Po is a critical determinant of ventilation. Currently, the relative importance of several putative chemoreceptor mechanisms for maintaining eupneic breathing and respiratory homeostasis is debated. Transcriptomic and anatomic evidence suggests that bombesin-related peptide Neuromedin-B () expression identifies chemoreceptor neurons in the retrotrapezoid nucleus (RTN) that mediate the hypercapnic ventilatory response, but functional support is missing. In this study, we generated a transgenic -Cre mouse and used Cre-dependent cell ablation and optogenetics to test the hypothesis that RTN neurons are necessary for the CO-dependent drive to breathe in adult male and female mice. Selective ablation of ∼95% of RTN neurons causes compensated respiratory acidosis because of alveolar hypoventilation, as well as profound breathing instability and respiratory-related sleep disruption. Following RTN lesion, mice were hypoxemic at rest and were prone to severe apneas during hyperoxia, suggesting that oxygen-sensitive mechanisms, presumably the peripheral chemoreceptors, compensate for the loss of RTN neurons. Interestingly, ventilation following RTN -lesion was unresponsive to hypercapnia, but behavioral responses to CO (freezing and avoidance) and the hypoxia ventilatory response were preserved. Neuroanatomical mapping shows that RTN neurons are highly collateralized and innervate the respiratory-related centers in the pons and medulla with a strong ipsilateral preference. Together, this evidence suggests that RTN neurons are dedicated to the respiratory effects of arterial Pco/pH and maintain respiratory homeostasis in intact conditions and suggest that malfunction of these neurons could underlie the etiology of certain forms of sleep-disordered breathing in humans. Respiratory chemoreceptors stimulate neural respiratory motor output to regulate arterial Pco and Po, thereby maintaining optimal gas exchange. Neurons in the retrotrapezoid nucleus (RTN) that express the bombesin-related peptide Neuromedin-B are proposed to be important in this process, but functional evidence has not been established. Here, we developed a transgenic mouse model and demonstrated that RTN neurons are fundamental for respiratory homeostasis and mediate the stimulatory effects of CO on breathing. Our functional and anatomic data indicate that -expressing RTN neurons are an integral component of the neural mechanisms that mediate CO-dependent drive to breathe and maintain alveolar ventilation. This work highlights the importance of the interdependent and dynamic integration of CO- and O-sensing mechanisms in respiratory homeostasis of mammals.
Topics: Humans; Mice; Male; Female; Animals; Carbon Dioxide; Bombesin; Respiration; Chemoreceptor Cells; Hypercapnia; Homeostasis; Mice, Transgenic; Oxygen; Neurons; Respiratory Center; Mammals
PubMed: 37290937
DOI: 10.1523/JNEUROSCI.0386-23.2023 -
The Journal of Biological Chemistry Mar 1996Amphibian bombesin is the prototypic peptide that defines the bombesin-like peptide family. In this paper we show that in the frog Bombina orientalis, there are actually... (Comparative Study)
Comparative Study
Amphibian bombesin is the prototypic peptide that defines the bombesin-like peptide family. In this paper we show that in the frog Bombina orientalis, there are actually 3 distinct forms of bombesin, and each of these peptides is an agonist with differing affinities for the known bombesin receptors. Oligonucleotides complementary to the 5'- and 3'-untranslated regions of the bombesin mRNA were used to amplify bombesin-related cDNAs from the skin, brain, and gut of B. orientalis. Three classes of cDNAs were found. One class encoded the previously characterized form of bombesin which has a Leu at position 13 ([Leu13]bombesin). The other two classes, respectively, encoded new bombesin-like peptides which we have designated as [Phe13]bombesin and [Ser3,Arg10,Phe13]bombesin ([SAP]bombesin). The existence of [SAP]bombesin in skin was confirmed by tandem mass spectrometry. Polymerase chain reaction analysis of genomic DNA showed the mRNAs for [Leu13]bombesin, [Phe13]bombesin, and [SAP]bombesin most likely arise from separate genes. Polymerase chain reaction analysis showed different patterns of tissue-specific expression for each form. [Leu13]Bombesin and [SAP]bombesin were predominantly expressed in skin, brain, and gut; [Phe13]bombesin was expressed only in brain, and [Leu13]bombesin predominated in oocytes. [SAP]Bombesin contained a cleavage site between residues 4 and 5, which if used would yield the peptide [SAP]bombesin(5-14) which has the sequence [Gln3,Arg6]neuromedin B. Thus a frog homolog of NMB could derive from the [SAP]bombesin prohormone. [Phe13]Bombesin, [SAP]bombesin, and [SAP]bombesin(5-14) were synthesized and their affinities for the mammalian bombesin-like peptide (GRP and NMB) receptors determined. These peptides acted as agonists for the GRP and NMB receptors, with relative potencies for the GRP receptor of [Leu13]bombesin > [Phe13]bombesin > [SAP]bombesin(5-14) > [SAP]bombesin and for the NMB receptor of [Phe13]bombesin > [SAP]bombesin(5-14) > [Leu13]bombesin > [SAP]bombesin. None of these peptides demonstrated high affinity binding for the BRS-3 receptor. The different receptor affinities and tissue distribution of these peptides suggests distinct physiologic roles and raises the possibility of as yet uncharacterized mammalian homologs of these new amphibian peptides.
Topics: Amino Acid Sequence; Animals; Anura; Base Sequence; Binding, Competitive; Bombesin; Female; Kinetics; Molecular Sequence Data; Multigene Family; Oocytes; Organ Specificity; Polymerase Chain Reaction; RNA, Messenger; Receptors, Bombesin; Recombinant Proteins; Sequence Homology, Amino Acid; Skin; Xenopus
PubMed: 8631814
DOI: 10.1074/jbc.271.13.7731 -
American Journal of Respiratory and... Jun 2006Bombesin-like peptides promote fetal lung development. Normally, levels of mammalian bombesin (gastrin-releasing peptide [GRP]) drop postnatally, but these levels are... (Comparative Study)
Comparative Study
RATIONALE
Bombesin-like peptides promote fetal lung development. Normally, levels of mammalian bombesin (gastrin-releasing peptide [GRP]) drop postnatally, but these levels are elevated in newborns that develop bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by arrested alveolarization. In premature baboons with BPD, antibombesin antibodies reduce lung injury and promote alveolarization.
OBJECTIVES
The present study tests whether exogenous bombesin or GRP given perinatally alters alveolar development in newborn mice.
METHODS
Mice were given peptides intraperitoneally twice daily on Postnatal Days 1-3. On Day 14 lungs were inflation-fixed for histopathologic analyses of alveolarization.
MEASUREMENTS AND MAIN RESULTS
Bombesin had multiple effects on Day 14 lung, when alveolarization was about half complete. First, bombesin induced alveolar myofibroblast proliferation and increased alveolar wall thickness compared with saline-treated control animals. Second, bombesin diminished alveolarization in C57BL/6 (but not Swiss-Webster) mice. We used receptor-null mice to explore which receptors might mediate these effects. Compared with wild-type littermates, bombesin-treated GRP receptor (GRPR)-null mice had increased interstitial fibrosis but reduced defects in alveolarization. Neuromedin B (NMB) receptor-null and bombesin receptor subtype 3-null mice had the same responses as their wild-type littermates. GRP had the same effects as bombesin, whereas neither NMB nor a synthetic bombesin receptor type 3 ligand had any effect. All effects of GRP were abrogated in GRPR-null mice.
CONCLUSIONS
Bombesin/GRP can induce features of BPD, including interstitial fibrosis and diminished alveolarization. GRPR appears to mediate all effects of GRP, but only part of the bombesin effect on alveolarization, suggesting that novel receptors may mediate some effects of bombesin in newborn lung.
Topics: Actins; Animals; Animals, Newborn; Bombesin; Cell Proliferation; Fibroblasts; Gastrin-Releasing Peptide; Gastrointestinal Agents; Injections, Intraperitoneal; Ligands; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurokinin B; Neurotransmitter Agents; Proliferating Cell Nuclear Antigen; Pulmonary Alveoli; Pulmonary Fibrosis; Receptors, Bombesin
PubMed: 16603607
DOI: 10.1164/rccm.200507-1014OC -
World Journal of Gastroenterology Jun 2008Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation,...
Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation, intestinal motility, blood flow, secretion, nutrient absorption and immune response. Based mainly on their well-established potent enterotrophic effect, numerous experimental studies investigated their potential positive effect on the atrophic or injured intestinal mucosa. These peptides proved to be effective mucosa-healing factors, but the potential molecular and cellular mechanisms for this action remained unresolved. In a recently published study (World J Gastroenterol 2008; 14(8): 1222-1230), it was shown that their protective effect on the intestine in experimentally induced inflammatory bowel disease was related to anti-inflammatory, antioxidant and antiapoptotic actions. These results are in close agreement with our previous studies on jaundiced and hepatectomized rats that showed a regulatory effect of bombesin and neurotensin on critical cellular processes such as enterocyte' proliferation and death, oxidative stress and redox equilibrium, tight junctions' formation and function, and inflammatory response. The pleiotropic effects of bombesin and neurotensin on diverse types of intestinal injury may justify their consideration for clinical trials.
Topics: Animals; Apoptosis; Bombesin; Cell Proliferation; Colitis; Disease Models, Animal; Intestinal Mucosa; Neurotensin; Neurotransmitter Agents; Oxidative Stress; Rats; Trinitrobenzenesulfonic Acid
PubMed: 18567096
DOI: 10.3748/wjg.14.3602