Disease relevance of Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• In the neuroblastoma/glioma hybrid cell line, NG108-15, LVV-hemorphin-7 and angiotensin IV competed for 125I-angiotensin IV binding in a biphasic fashion with IC50 values of 1.2 x 10(-10) and 1.1 x 10(-9) M for the high-affinity site, respectively, and 6.7 x 10(-8) and 1.5 x 10(-8) M for the low-affinity site, respectively [1].
• LVV-hemorphin-7 was not identified in BAL fluid from seven additional patients with non-small cell lung cancer, indicating that the formation of the peptide is unlikely to be of any diagnostic significance [2].
• The decapeptide Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe was isolated in high yield (1.5 nmol/ml) from bronchoalveolar lavage (BAL) fluid from a patient with an adenocarcinoma of the lung [2].

Psychiatry related information on Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia [3].

High impact information on Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• The current finding suggests that LVV-hemorphin-7 is a functional peptide in the central nervous system and in view of its abundance in neural tissue, compared with angiotensin IV, may be of significant physiological importance [1].
• Recently, we found that LVV-hemorphin-7, a fragment of beta globin, is an abundant peptide in the brain and binds to the AT4 receptor with high affinity and specificity [1].
• A globin fragment, LVV-hemorphin-7, induces [3H]thymidine incorporation in a neuronal cell line via the AT4 receptor [1].
• This peptide is identical to the amino acid sequence 30-39 of sheep betaA- and betaB-globins and has previously been named LVV-hemorphin-7 [4].
• Binding was displaced with high potency by the "AT4 receptor" ligands (Ang IV > divalinal1-Ang IV approximately LVV-hemorphin-7 approximately LVV-hemorphin-6 > Ang (3-7) > Ang III > Ang (4-8)) but not by AT1/AT2 receptor antagonists [5].

Biological context of Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• Moreover, taking LVV-hemorphin-7 as model compound, we evaluated its biological effect on blood pressure of anaesthetized rats [6].
• LVV-hemorphin-7 was the first generated, at a degree of hydrolysis (DH), as low as 4% [7].
• Intrarenal infusion of LVV-hemorphin-7 (10, 100, and 1,000 pmol/min) had no significant effect on renal blood flow in the infused and noninfused kidneys, or on mean arterial pressure or heart rate [8].

Anatomical context of Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• Enzymatic activity in CHO-K1 cell membranes was competitively inhibited upto 94% by Ang IV and other "AT4 receptor" ligands (Ang IV > Ang III approximately divalinal1-Ang IV approximately Ang (3-7) approximately LVV-hemorphin-7 > Ang (4-8) approximately LVV-hemorphin-6) [5].
• Angiotensin IV and LVV-hemorphin-7 both potentiated depolarisation-induced [(3)H]ACh release from the rat hippocampus in a concentration-dependent manner with the maximal dose (10(-7)M) of each inducing an increase of 45+/-7.5% (P<0.01) and 95.8+/-19% (P<0.01) above control, respectively [9].
• Rapid analysis of endogenous LVV-hemorphin-7 in cerebrospinal fluid by size-exclusion chromatography and electrospray ionization mass spectrometry [10].
• High-performance liquid chromatography (HPLC) combined with electrospray ionisation mass spectrometry (ESI-MS) allows identification of degradation products resulting from incubation of hemorphin-7 peptides (LVV-hemorphin-7, VV-hemorphin-7 and hemorphin-7) with subcellular fractions isolated from rat brain tissue [11].
• In vitro metabolism of LVV-Hemorphin-7 by renal cytosol and purified prolyl endopeptidase [12].

Associations of Leu-val-val-tyr-pro-trp-thr-gln-arg-phe with other chemical compounds

• 1. The human orphan G-protein coupled receptor bombesin receptor subtype 3 (hBRS-3) was screened for peptide ligands by a Ca(2+)mobilization assay resulting in the purification and identification of two specific ligands, the naturally occurring VV-hemorphin-7 (VV-H-7) and LVV-hemorphin-7 (LVV-H-7), from human placental tissue [13].
• All LVV-hemorphin-7 analogs tested, except for Leu-Val-Val-Tyr, inhibit the cleavage of the synthetic substrate, leucine beta-naphthylamide, by IRAP, with K(i) values between 56 and 620 nM [14].

Gene context of Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• We find that the Val(3) residue is crucial for LVV-hemorphin-7 binding to IRAP, whereas the C-terminal domain seems to play a minor role [14].
• Their primary structure and accurate molecular weights, determined by amino acid analysis and fast atom bombardment (FAB) mass spectrometry, were identical to fragments 31-40 (LVV-hemorphin-7) and 32-40 (VV-hemorphin 7) of the beta-chain of bovine hemoglobin [15].
• Our results indicate that VV-hemorphin-7 and LVV-hemorphin-7 exhibit a lesser potency both in GPI and binding tests [16].

Analytical, diagnostic and therapeutic context of Leu-val-val-tyr-pro-trp-thr-gln-arg-phe

• In vitro metabolism of LVV-hemorphin-7 in human plasma studied by reversed-phase high-performance liquid chromatography and micro-electrospray mass spectrometry [17].
• A microdialysis probe (flow rate 0.4 microL/min) was used to both introduce LVV-hemorphin-7 into the striatum of the brain (1.0 pmol/microL) or the venous blood (10 pmol/microL) and to collect the metabolic products [18].
• In this study, we developed a rapid technique to analyze LVV-hemorphin-7 in CSF fluid from a patient with cerebrovascular bleedings using a combination of size-exclusion chromatography and electrospray ionization mass spectrometry [10].
• Two peptides, VV-hemorphin-7 and LVV-hemorphin-7, were resolved by a combination of size exclusion and reversed phase HPLC [19].

References