Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dispersed newborn hamster lung cells were established in vitro in a defined, low-serum growth medium. Neuroendocrine markers (immunohistochemistry for bombesin/gastrin-releasing peptide and calcitonin) revealed a cellular predominance of pulmonary neuroendocrine (PNE) cells. While the supernatant concentration remained stable, the concentration of PNE cell immunoreactive calcitonin (iCT) gradually declined over 4 weeks. Supplementation of the medium with nicotine for 3 weeks prevented this decline in cellular iCT. Concurrently, the number of cells and [3H]thymidine incorporation were significantly increased. The stimulatory effect of chronic nicotine was reversed by the coadministration of the nicotinic antagonist hexamethonium. In another set of experiments, prior multiple transplacental nicotine pretreatments resulted in a significant increase in iCT in the lungs of newborns; when these lungs were subsequently placed in cell culture without nicotine, despite the higher concentration of iCT, there was a drop in iCT similar to that observed in the control culture. In contrast, in vivo, the lung iCT remained significantly elevated at 1 week post-parturition. Cell culture supernatants were analyzed at week 4 for the evoked release of iCT; cholinergic-nicotinic agonists promptly increased the supernatant iCT, which was blocked by nicotinic but not by muscarinic antagonists. We suggest that this in vitro system provides a useful tool to study directly the PNE cell. The acute and chronic effects of nicotine are most likely related to stimulation of cholinergic-nicotinic receptors on iCT-containing PNE cells.
Anat Rec 1993 May
PMID:Cholinergic-nicotinic control of growth and secretion of cultured pulmonary neuroendocrine cells. 850 98

Human pulmonary neuroendocrine cells produce a variety of hormones, including mammalian bombesin (BN) or gastrin-releasing peptide (GRP). Neuroendocrine cell hyperplasia and increased release of BN-like peptides occur in several diseases of the airways, including chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia. Growth stimulation of human bronchial epithelial cells by BN, as measured in a colony-forming assay, has been reported previously (Willey et al.:Exp. Cell Res. 153:245-248, 1984). In a follow-up to this report, we examined the response of human bronchial epithelial (HBE) cells to BN or GRP in a similar system, using cells derived from 13 human tissue donors. A stimulatory response (increased colony-forming efficiency) was found in cultures from 8 donors, including 3 with COPD. Statistical significance was found for the data from 5 of these 8 donors. The other 5 donors, 1 normal and 4 lung cancer patients, showed inhibition of colony formation by BN or GRP. Statistical significance was found for 3 of these donors. The ability of BN analogs to modulate BN stimulation was examined in cells from a donor with COPD. [psi Leu13,Leu14] BN(1-14), a BN antagonist, blocked the stimulation induced by BN. [D-Cpa6,psi Leu13,Phe14] BN(6-14), a mixed agonist-antagonist, showed partial agonist activity in HBE cells. [D-Phe1,Leu8,9] Litorin, an agonist, also showed agonist activity in a colony-forming assay with cells from these donors. These results indicate that responsiveness to BN/GRP may vary widely in the human population. Responsiveness may be heightened in disease states involving a proliferation of neuroendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Anat Rec 1993 May
PMID:Effects of bombesin and gastrin-releasing peptide on human bronchial epithelial cells from a series of donors: individual variation and modulation by bombesin analogs. 850 11

Fetal pulmonary neuroendocrine cells (PNECs) contain abundant gastrin-releasing peptide (GRP, mammalian bombesin-like peptide [BLP]). Previously, addition of bombesin resulted in increased fetal lung growth and maturation in utero and in organ cultures. A monoclonal antibody (mAb) to bombesin (2A11) blocked baseline automaturation of lung organ cultures in serum-free medium. In the present study, we analyze lung development following daily in utero administration of 2A11 from gestational days 15-18. Fetal lung treated with 2A11 and then harvested on day 18 demonstrated a dose-dependent decrease in surfactant phospholipid synthesis compared to controls treated with MOPC, an unreactive mAb. However, 2A11-treated fetal lung harvested on day 17 showed paradoxical increases in 3H-choline incorporation into saturated phosphatidylcholine, 3H-thymidine incorporation into DNA, and relative numbers of differentiated type II pneumocytes. In serum-containing day 17 lung organ cultures, 2A11 stimulated choline and thymidine incorporation. Since epidermal growth factor (EGF) is the only agent besides bombesin known to stimulate both fetal lung growth and maturation, we added EGF to serum-free cultures and reconstituted the stimulatory effects. A murine EGF receptor mAb (ERA) blocked 2A11-induced lung growth and maturation in serum-containing cultures, and this effect was overcome by adding EGF. In vivo, ERA also blocked stimulatory effects of 2A11 in fetal lung on day 17. These observations suggest that EGF receptor up-regulation may maintain lung growth and maturation if BLP levels are diminished on day 17. Nonetheless, BLPs appear to be involved in lung maturation on day 18, supporting a role for PNECs in normal lung development.
Anat Rec 1993 May
PMID:Anti-bombesin monoclonal antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures. 850 13

Bombesin-like peptides (BLPs) are important regulators of lung development and may also act as autocrine growth factors in lung tumors. We have previously demonstrated expression of mRNA for the three BLP receptor subtypes (neuromedin B [NMB]) receptor, gastrin-releasing peptide [GRP] receptor, and bombesin receptor subtype 3 [BRS-3]) in human non-small cell lung carcinoma (NSCLC) cell lines and bronchial biopsies using the reverse transcription-polymerase chain reaction (RT-PCR; DeMichele, et al. Am. J. Respir. Cell Mol. Biol. 1994; 11:66-74). We have also previously found that growth responses to BLPs could be elicited in some, but not all, cultures of human bronchial epithelial (HBE) cells (Siegfried, et al. Anat. Rec. 1993; 236:241-247). In this report, we utilized RT-PCR to demonstrate mRNA expression of BLP receptor subtypes in cultured HBE cells and also assessed the response of these cultures to BLPs in proliferation assays. The pattern of mRNA expression was correlated with proliferative response, and the results were also analyzed in relation to smoking history and pulmonary function of the subjects studied. Our results suggest that expression of mRNA for the GRP receptor is associated with a long smoking history (> 25 pack-years [PY], p = 0.02). This association was related to past tobacco exposure, regardless of whether the subjects were still active smokers at the time of tissue procurement. Responsiveness to GRP and NMB in proliferation assays was also found only in those HBE cultures with expression of mRNA for at least one of the known receptors for BLPs, and there was a significant association between expression of mRNA for the GRP receptor and proliferative response to both GRP and NMB (p = 0.048). HBE cultures from subjects with a greater than 25 PY smoking history were also more likely to respond to BLPs in the proliferation assays than cells from subjects with less than a 25 PY history (10 of 16 versus 1 of 7, p = 0.06). Cultures of HBE cells from four of the five subjects with severe obstructive lung disease gave a positive response to GRP and NMB in proliferation assays, compared to five of fifteen without severe obstructive lung disease, but this difference was not significant (p = 0.13). These results suggest there is an increased likelihood of expression of the GRP receptor mRNA in the respiratory epithelium of some individuals with a history of prolonged tobacco exposure, and that expression of the GRP receptor mRNA is accompanied by responsiveness to the mitogenic effects of BLPs. These effects appear to persist after smoking cessation.
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PMID:Expression of mRNA for gastrin-releasing peptide receptor by human bronchial epithelial cells. Association with prolonged tobacco exposure and responsiveness to bombesin-like peptides. 927 10

Many gastrointestinal and pancreatic functions are under strong modulatory control by the brain via the vagus nerve. To start identifying location and neurochemical phenotype of the enteric neurons receiving functional vagal efferent input, we activated vagal preganglionic neurons either by electrical or chemical stimulation and examined the expression of phosphorylated CREB (c-AMP response element binding protein) and the immediate early gene c-Fos. There was no spontaneous expression of both markers in the pancreas and considerable spontaneous expression of p-CREB but not Fos in the upper GI-tract. Unilateral electrical vagal stimulation-induced p-CREB was found in 40% of neurons in the head of the pancreas. Fos expression was found in 70-90% of neurons in the esophagus and stomach, in 20-30% of myenteric plexus neurons and 5-15% in submucosal neurons of the proximal duodenum. Double-labeling experiments showed that a majority of pancreatic neurons and about 25-35% of neurons in the stomach and duodenum contain NADPH-diaphorase and that many of these receive functional vagal input. Other neurons that can be vagally activated contain gastrin-releasing peptide or calretinin. Chemical stimulation of the dorsal surface of the caudal brainstem with the stable TRH analog RX77368 resulted in selective activation of vagal efferents with expression of Fos in a small number of gastric myenteric plexus neurons. The results demonstrate the suitability of this method to investigate magnitude and local distribution of vagal input to the enteric nervous system as well as specificity of its neurochemically coded pathways. They represent the first step in the identification of function-specific units of parasympathetic vagal outflow.
Anat Rec 2001 01 01
PMID:Vagal-enteric interface: vagal activation-induced expression of c-Fos and p-CREB in neurons of the upper gastrointestinal tract and pancreas. 1114 26