Disease relevance of Tff2

• Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis [1].
• In nucleus basalis neurons, substance P (SP) causes a slow excitation, mediated through a pertussis toxin-insensitive G protein, by suppressing an inward rectifier K+ channel [2].
• SP is the primary mediator of an axon reflex mediating neurogenic inflammation in the intestine [3].
• Therefore, this study examines the effect of SP on capsaicin-induced mucosal hyperemia and mast cells [4].
• Conversely, treatment with nerve growth factor (NGF) increased both ganglionic SP and total ganglion protein [5].

Psychiatry related information on Tff2

• In these cells, the peak response latency was significantly longer to Ang II than to SP (59.5 +/- 4.7 versus 26.5 +/- 2.4 seconds, p less than 0.0001) [6].
• Only (D-Pro4, D-Trp7,9,10) SP (4-11) was found to attenuate the drug-induced increases in motor activity, indicating that it is a substance P antagonist with activity in the CNS [7].
• In the second experiment, a facilitation of inhibitory avoidance learning was obtained by injection of RA-octil or SP unilaterally into the basal forebrain immediately after the learning trial [8].
• If SP is coreleased with acetylcholine, the additive actions of the two neurotransmitters might heighten the excitability of postsynaptic PRF neurons and ensure the initiation and maintenance of REM sleep [9].
• In contrast, low pain threshold correlated with decreased IR-SP and IR-ME [10].

High impact information on Tff2

• For example, footshock stress can activate rat mesocortical DA cells but does not alter nigrostriatal DA turnover, while also decreasing substance P (SP) concentrations in the midbrain interpeduncular nucleus and in the adjacent ventral tegmental area (VTA), but not in the substantia nigra (SN) [11].
• SP antagonists now available are neurotoxic and of questionable efficacy, we therefore used monoclonal antibody against SP [11].
• Veratridine prevented the increase in SP concentration in adult ganglia, and tetrodotoxin blocked the veratridine effect, suggesting that membrane depolarization and sodium influx prevented the rise in the SP content of adult ganglia as well as of neonatal ganglia [12].
• The effect of age on the plasticity of the putative peptide neurotransmitter substance P (SP) was examined in the rat superior cervical sympathetic ganglion [12].
• These results indicate that a diffusible messenger mediates the SP effect, that its signal transduction involves phosphorylation by PKC, and that dephosphorylation by a serine/threonine protein phosphatase mediates its recovery [2].

Chemical compound and disease context of Tff2

• In locus coeruleus neurons, substance P (SP) suppresses an inwardly rectifying K+ current via a pertussis toxin-insensitive guanine nucleotide binding protein (G protein; GnonPTX), whereas somatostatin (SOM) or [Met]enkephalin (MENK) enhances it via a pertussis toxin-sensitive G protein (GPTX) [13].
• After nTS injection of the NK1-selective SP antagonist CP-96,345 (30 pmol in 60 nL), Ang II-induced hypotension was blocked in both groups, as was the pressor component in hypertensive rats [14].
• Low doses of either angiotensin (Ang) II or substance P (SP) microinjected into the medial nucleus tractus solitarii (NTS) produce hypotension and bradycardia, mimicking activation of the baroreceptor reflex [6].
• In the trigeminal ganglion and in the dorsal root ganglion at level C2, one-third of the TB-labeled nerve cell bodies were CGRP-immunoreactive, while only few nerve cell bodies contained SP [15].
• We now report that multiple injections of sub-threshold doses of SP into the foot pad of a hind paw of rats pre-treated with indomethacin induced a long-lasting hyperalgesia, sensitizing the paw to further challenges with small doses of SP, dopamine or prostacyclin [16].

Biological context of Tff2

• SP gene expression was localized by Northern blotting and in situ hybridization in the adult and fetal rat digestive tract [17].
• We conclude that CDH+TO partially reverses effects of CDH; it corrects the pulmonary hypoplasia and restores type I cell differentiation but adversely affects SP expression in type II cells [18].
• In contrast to trefoil secretory rates, the steady-state synthesis of both TFF1/pS2 and TFF2/SP was unchanged after omeprazole treatment, implying both a large cellular pool of processed peptide and rapid secretion [19].
• Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were used to assess the expression of NK(1)Rs and/or SP in samples of colon, spinal cord, and dorsal root ganglia [20].
• The average number of high affinity SP binding sites per cell was 1.0 x 10(5) and 0.3 x 10(5) for the full-length and the truncated SP receptor, respectively [21].

Anatomical context of Tff2

• SP predominates in the gastric antrum as a 12 kDa form [22].
• Both peptides are distributed in the apical secretory compartment of antral mucus cells (SP) and goblet cells (ITF), and on the lumenal surface [22].
• Abundant SP immunoreactivity was seen in the lumen of the gastric glands and the mucus layer adherent to the gastric mucosa, indicating luminal secretion [17].
• This study aimed to determine the structure and distribution of SP expression in the rat gastrointestinal tract [17].
• The expression of SP in rats (rSP) was detected by RT-PCR in the intact mucosa and during all tested time periods reaching a peak at 4 h after the stress [23].

Associations of Tff2 with chemical compounds

• In capsaicin-pretreated rats, the levels of substance P (SP) in bone marrow fluid were markedly reduced in comparison with the vehicle group (13.1+/-4.5pg/ml versus 47.3+/-5.5pg/ml, p<0.05) [24].
• METHODS: Rats (n=8) were given either omeprazole (30 mg/kg per day; p.o.) or inert carrier for 1 week, and the effects on synthesis and peptide expression of the gastric trefoil peptides, TFF1/pS2 and TFF2/SP, were compared [19].
• Preservation of mast cells in SP-treated rats was linearly correlated to increased mucosal blood flow after exposure to capsaicin [4].
• This inhibitory action of SP was not blocked by atropine or hexamethonium, suggesting that a cholinergic mechanism was not involved [25].
• RNase protection experiments indicated that the major message in the SCG is the beta-PPT mRNA, encoding both SP and neurokinin A peptide regions [26].

Regulatory relationships of Tff2

• High levels of SP mRNA were expressed in the fetal stomach before gastrin and somatostatin expression [17].

Other interactions of Tff2

• Increased lung distension (due to CDH+TO) reduced expression of SP mRNAs and pro-SP-C and TTF-1 proteins and enhanced expression of RTI(40) (mRNA and protein; P < 0.05 for all) [18].
• Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat [27].

Analytical, diagnostic and therapeutic context of Tff2

• Expression of the SP peptide was localized by immunocytochemistry and Western blot analysis [17].
• The trefoil pancreatic spasmolytic polypeptide (PSP) was tested for growth activity in vitro on epithelial cells and in vivo following intragastric or intravenous infusion in parenterally fed intact rats [28].
• Much of the research into the localization of the spasmolytic polypeptide has relied on hybridization in situ to detect its mRNA, due to the absence of a suitable antibody [29].
• Bilateral microinjections of the neurokinin-1 receptor antagonist [2-cyclopropoxy-5-(5-(trifluoromethyl)tetrazol-1-yl)benzyl]-(2-phenylpiperidin-3-yl)amine into the MeA blocked the stress-induced anxiogenic-like effect, supporting a functional significance of enhanced SP release [30].
• Evidence for a potent inhibitory effect of SP on 5alpha-DHP and 3alpha,5alpha-THP formation in the SC was provided by combining pulse-chase experiments using [3H]progesterone as precursor, HPLC, recrystallization of [3H]metabolites to constant specific activity, and continuous flow detection of radioactive steroids [31].

References