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[Comparison of vasorelaxing actions of vasonatrin peptide, C-type natriuretic peptide and atrial natriuretic peptide].

The vasorelaxing effects of vasonatrin peptide (VNP), C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) on isolated rat pulmonary artery, abdominal aorta and celiac vein were measured by in vitro perfusion. The results showed that VNP, CNP and ANP caused concentration-dependent relaxation in isolated rat pulmonary artery, abdominal aorta and celiac vein with endothelium or without endothelium. The maximal responses (Rmax) of VNP were (76 +/- 17)%, (51 +/- 14)% and (62 +/- 14)% in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, whereas those of CNP were (31 +/- 8)%, (22 +/- 7)% and (41 +/- 8)%, and ANP (38 +/- 10)%, (41 +/- 10)% and (11 +/- 4)%. The median effective concentration (EC50) of VNP were 16 +/- 11, 35 +/- 18 and 12 +/- 8 nmol/L in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, while those of CNP were 148 +/- 112, 299 +/- 84 and 14 +/- 12 nmol/L, and ANP 66 +/- 47, 16 +/- 15 and 909 +/- 445 nmol/L. VNP were more effective than CNP and ANP, and the differences were statistically significant (P < 0.05-0.01). The potency of these peptides for relaxing the blood vessels can be summarized as: VNP > ANP > or = CNP for pulmonary artery; VNP > ANP > CNP for abdominal aorta; VNP > CNP > ANP for celiac vein. There was no significant difference between vessels with intact endothelium and those denuded of endothelium (P > 0.05).

Animals↗

[Basic peptides in bee venom, III. Synthesis of peptide fragments from the sequence of the mast-cell-degranulating peptide (author's transl)].

The synthesis by conventional methods of the following three peptides is described: MCD(8-11) Boc-His(Trt)-Val-Ile-Lys(Z) (III) MCD(5-7) Boc-Cys(SiPr)-Lys(Z)-Arg(Tos) (IV) and MCD(1-4) Boc-Ile-Lys(Z)-Cys(Trt)-Asn(Mbh) (V). These peptides are fragments of the mast cell degranulating peptide from bee venom. The purity of the fragments synthesized was examined by thin-layer chromatography, amino acid and elementary analysis. Including the fragments Boc-Lys(Z)-Ile-Cys(SiPr)-Gly-Lys(Z) (I) and Boc-Pro-His(Trt)-Ile-Cys(Trt)-Arg(Tos) (II), which were described earlier, the synthesis of the mast-cell-degranulating peptide on a polyethylene-asparagine support appears possible.

Amino Acid Sequence↗

Levitide, a neurohormone-like peptide from the skin of Xenopus laevis. Peptide and peptide precursor cDNA sequences.

A novel peptide, levitide, less than Glu-Gly-Met-Ile-Gly-Thr-Leu-Thr-Ser-Lys-Arg-Ile-Lys-Gln-NH2 has been isolated from skin secretions of the South African frog Xenopus laevis and sequenced by fast atom bombardment mass spectrometry. Synthetic oligonucleotides were used as probes to screen a X. laevis skin cDNA library for species coding for preprolevitide. Two such clones were detected and their sequences are reported here. Preprolevitide is 88 residues long, exhibits a putative signal sequence at the amino terminus, and contains the levitide peptide at the carboxyl terminus. The levitide precursor shows a striking nucleotide and amino acid (86%) sequence homology with the precursor of xenopsin, a biologically active octapeptide from Xenopus skin, and also encodes a 25-residue amphipathic peptide that is released by processing at a single arginine residue.

Amino Acid Sequence↗

Atrial natriuretic peptide, brain natriuretic peptide and c-type natriuretic peptide: effects on testicular microcirculation and immunohistochemical localization.

The effect of local injection of atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides and an ANP antagonist (HS-142-1) on testicular microcirculation and vasomotion was studied using laser Doppler flowmetry. The natriuretic peptides were also localized immunohistochemically within the testis. ANP, BNP-32, CNP-22 and CNP-53 all caused a dose-related increase in testicular blood flow. The effect of ANP was blocked by concomitant injection of the ANP antagonist. Immunoreactive (ir) CNP and ir BNP were found in Leydig cells whereas in ANP was observed in the seminiferous tubules. It is suggested that the natriuretic peptides could play a role in local regulation of the testicular microcirculation.

Animals↗

Blockade and reversal of spinal morphine tolerance by peptide and non-peptide calcitonin gene-related peptide receptor antagonists.

This study examined the effects of the peptide CGRP receptor antagonist CGRP(8-37) and the newly-developed non-peptide CGRP receptor antagonist BIBN4096BS for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. Repeated administration of intrathecal morphine (15 microg), once daily, produced a progressive decline of antinociceptive effect and an increase in the ED(50) value in the tailflick and paw pressure tests. Co-administration of CGRP(8-37) (4 microg) or BIBN4096BS (0.05, 0.1 microg) with morphine (15 microg) prevented the decline of antinociceptive effect and increase in ED(50) value in the tailflick test. Intrathecal administration of the CGRP receptor antagonists did not alter the baseline responses in either tests. Acute CGRP(8-37) also did not potentiate the acute actions of spinal morphine. In animals rendered tolerant to intrathecal morphine, subsequent administration of CGRP(8-37) (4 microg) with morphine (15 microg) partially restored the antinociceptive effect and ED(50) value of acute morphine, reflecting the reversal of tolerance. Animals tolerant to intrathecal morphine expressed increased CGRP and substance P-like immunostaining in the dorsal horn of the spinal cord. The increase in CGRP, but not substance P-like immunostaining, was blocked by a co-treatment with CGRP(8-37) (4 microg). In animals already tolerant to morphine, the increase in CGRP but not substance P-like immunostaining was partially reversed by CGRP(8-37) (4 microg). These data suggest that activation of spinal CGRP receptors contributes to both the development and expression of spinal opioid tolerance. CGRP receptor antagonists may represent a useful therapeutic approach for preventing as well as reversing opioid tolerance.

Animals↗

Urocortin, a newly identified corticotropin-releasing factor-related mammalian peptide, stimulates atrial natriuretic peptide and brain natriuretic peptide secretions from neonatal rat cardiomyocytes.

The effect of urocortin (UCN), a recently characterized mammalian member of corticotropin-releasing factor (CRF)-related peptide and a putative endogenous ligand for CRF type 2 beta receptor in the regulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) release, was investigated using cultured neonatal rat cardiomyocytes. Treatment with UCN (10(-10)-10(-6)M) resulted in significant increase in ANP and BNP secretions, and the effect of UCN on ANP and BNP secretions was more potent than that of CRF on an equimolar basis. The effect of UCN (10(-7)M) was completely blocked by alpha-helical CRF (9-41), a specific CRF type 2 receptor antagonist. The effect of UCN (10(-7)M) was not only blunted by cAMP-dependent protein kinase A (PKA) inhibitor, H-89 (10(-5)M), but also diltiazem (10(-7)M), a voltage-dependent Ca2+ channel blocker. Further, UCN stimulated cAMP production in cardiomyocytes. Also, UCN (10(-7)M) itself stimulated [3H]leucine uptake into neonatal rat cardiomyocytes and potentiated endothelin-1-induced increase of [3H]leucine uptake. These results suggest that activation of CRF type 2 receptor, especially type 2 beta receptor, with UCN induces ANP and BNP secretions, at least in part, via PKA pathway during cardiac hypertrophy.

Animals↗

Pituitary adenylate cyclase-activating peptide (PACAP), a new vasoactive intestinal peptide (VIP)-like peptide in the respiratory tract.

Pituitary adenylate cyclase-activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like peptide recently isolated from ovine hypothalami. Nerve fibers displaying PACAP immunoreactivity were found in the respiratory tract of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. A moderate supply of PACAP-immunoreactive fibers was seen in the nasal mucosa of guinea pigs. Few to moderate numbers of PACAP-containing fibers occurred in the tracheo-bronchial wall of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. The fibers were distributed beneath the epithelium, around blood vessels and seromucous glands, and among bundles of smooth muscle. In the lungs, the immunoreactive fibers were observed close to small bronchioli. A few PACAP-immunoreactive nerve cell bodies were seen in the sphenopalatine and otic ganglia of guinea pigs. Simultaneous double immunostaining of the respiratory tract of sheep and ferrets revealed that all PACAP-containing nerve fibers stored VIP. We suggest that neuronal PACAP may take part in the regulation of smooth muscle tone and glandular secretion.

Animals↗

Effects of peptides: a cross-listing of peptides and their central actions published in the journal Peptides from 1994 through 1998.

Effects of peptides on the central nervous system are presented in two ways so as to provide a cross-listing. In the first table, the peptides are listed alphabetically. In the second table, the central nervous system effects are arranged alphabetically. No longer can there be any doubt that peptides affect the central nervous system, sometimes in several ways.

Peptides↗

Lipid headgroup spacing and peptide penetration, but not peptide oligomerization, modulate peptide-induced fusion.

In this study, the mechanism by which an amphipathic negatively charged peptide consisting of 11 amino acids (WAE) induces fusion of liposomal phosphatidylcholine membranes is investigated. WAE-induced fusion, which only occurs when the peptide is covalently attached to the bilayer, shows a highly remarkable dependence on naturally occurring phosphatidylcholine species. The initial rate of fusion increased in the order 1-palmitoyl 2-arachidonoyl PC (PAPC) > 1-palmitoyl 2-oleoyl PC (POPC) > 1-stearoyl 2-oleoyl PC (SOPC) > dioleoyl PC (DOPC) > egg yolk PC. Interestingly, the susceptibility of the various PC species toward WAE-induced fusion matched a similar order of increase in intrinsic lipid headgroup spacing of the target membrane. The degree of spacing, in turn, was found to be related to the extent by which the fluorescence quantum yield of the Trp residue increased, which occurred upon the interaction of WAE with target membranes. Therefore, these results demonstrate an enhanced ability for WAE to engage in hydrophobic interactions when headgroup spacing increases. Thus, this latter parameter most likely regulates the degree of penetration of WAE into the target membrane. Apart from penetrating, WAE oligomerizes at the site of fusion as revealed by monitoring the self-quenching of the fluorescently derivatized lipid anchor to which WAE is attached. Clustering appears specifically related to the process of membrane fusion and not membrane aggregation. This is indicated by the fact that fusion and clustering, but not aggregation, display the same strict temperature dependence. However, evidence is presented indicating that clustering is an accompanying event rather than a prerequisite for fusion. The notion that various biologically relevant fusion phenomena are accompanied by protein clustering and the specific PC-species-dependent regulation of membrane fusion emphasize the biological significance of the peptide in serving as a model for investigating mechanisms of protein-induced fusion.

Egg Yolk↗

Effects of dipyridamole and adenosine on vasoactive peptides calcitonin gene-related peptide and atrial natriuretic peptide in humans: role of sympathetic activation.

1. It has been observed that dipyridamole (DIP) administration produces equivalent cardiovascular effects at lower systemic adenosine (ADO) plasma concentrations than those obtained with exogenous ADO infusion. This observation led to the identification of DIP for additional 'ischaemia-inducing' mechanisms, possibly based on sympathetic activation. 2. In turn, exogenous ADO administration has proven to elicit a complex neurohumoral response, including an increase in the plasma concentration of catecholamines, associated with augmented levels of the vasoactive peptides calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP). More particularly, increases in CGRP seem to be dependent on sympathetic activation, while changes in ANP do not. 3. In order to clarify some aspects of the activity of DIP on neurohumoral systems, the effects of administration of DIP and ADO on plasma levels of noradrenaline (NA), CGRP and ANP were studied in healthy volunteers. Haemodynamic parameters were also monitored. 4. Infusion of exogenous ADO produced plasma levels of ADO as high as 1893+/-386 nmol/L, together with a significant increase in plasma levels of CGRP, ANP and NA. Similarly, the infusion of DIP produced augmented plasma concentrations of the examined parameters, with a peak plasma ADO concentration of 470+/-49 nmol/L. 5. At a given ADO plasma concentration of 450+/-10 nmol/L, the increase in CGRP and NA levels with DIP infusion was significantly higher than that observed following the infusion of ADO, whereas the increase in the plasma concentration of ANP following DIP infusion was very similar to that seen following ADO infusion. 6. The physiological background of these findings is based on evidence that DIP displays a greater sympathoexcitatory activity than does exogenous ADO and only the increase in plasma CGRP seems to be mediated, although indirectly, by beta-adrenoceptor stimulation. The exact mechanism of DIP-dependent sympathetic activation remains to be elucidated.

Adenosine↗

A P5 peptide that is homologous to peptide 10 of OprF from Pseudomonas aeruginosa enhances clearance of nontypeable Haemophilus influenzae from acutely infected rat lung in the absence of detectable peptide-specific antibody.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen associated with otitis media and the exacerbation of chronic bronchitis. This study reports the vaccine potential of three peptides representing conserved regions of the NTHi P5 outer membrane protein which have been fused to a promiscuous measles virus F protein T-cell eptitope (MVF). The peptides correspond to a region in surface loop one (MVF/L1A), the central region of loop four (MVF/L4), and a C-terminal region homologous to peptide 10 of OprF from Pseudomonas aeruginosa (MVF/H3). Immunization of rats with MVF/H3 was the most efficacious in significantly reducing the number of viable NTHi in both the broncho-alveolar lavage fluid (74%) and lung homogenates (70%), compared to control rats. Importantly, despite significantly increased rates of clearance, immunization with MVF/H3 elicited poor antibody responses, suggesting that cell-mediated rather than humoral responses play an important role in the enhanced clearance of NTHi in this model.

Acute Disease↗

Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.

BACKGROUND: Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. METHODS AND RESULTS: Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%. CONCLUSIONS: These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.

Aged↗

A homolog of mammalian PRL-releasing peptide (fish arginyl-phenylalanyl-amide peptide) is a major hypothalamic peptide of PRL release in teleost fish.

Two PRL-releasing peptides (PrRP20 and PrRP31) were recently identified from mammalian hypothalamus by an orphan receptor strategy, and a C-terminal RF (arginyl-phenylalamyl-) amide peptide (RFa), structurally related to mammalian PrRP, was also identified from the brain of the Japanese crucian carp (C-RFa) by an intestine-contracting assay. However, to date there have been no reported studies that have examined the PRL-releasing effects of RFa in fish. In the present study we determined the cDNA, primary structure, and function of a homolog of the mammalian PrRP20 in the chum salmon, Oncorhynchus keta. An RFa cDNA encoding a preprohormone of 155 amino acids was cloned from the hypothalamus of chum salmon by 3'- and 5'-rapid amplification of cDNA ends. A native RFa was purified from an acid extract of salmon hypothalami by a Sep-Pak C(18) cartridge, affinity chromatography using anti-synthetic C-RFa, and reverse phase HPLC on an ODS-120T column. The salmon RFa proved to be identical with C-RFa on the basis of elution position on reverse phase HPLC. Immunocytochemical staining in rainbow trout, Oncorhynchus mykiss, revealed that C-RFa-immunoreactive cell bodies were located in the posterior part of hypothalamus and C-RFa-immunoreactive fibers were abundant from the hypothalamus to the ventral telencephalon. A small number of immunoreactive fibers were projected to the pituitary and terminated close to the PRL cells in the rostral pars distalis and to the somatolactin (SL) cells in the pars intermedia. The hypophysiotropic effects of the fish homolog were determined on the release of PRL, SL, and GH from the pituitary of the rainbow trout. Plasma PRL and SL levels were increased at 3 and 9 h, respectively, after ip injection of the synthetic C-RFa into the rainbow trout at doses of 50 and 500 ng/g body weight. In contrast, plasma GH levels were decreased after 1 h at 500 ng/g body weight. Perifusion of the trout pituitaries with synthetic C-RFa at concentrations of 10 pM to 100 nM demonstrated maximum PRL release at 100 pM and maximum SL release at 10 and 100 nM. However, GH release was not affected. These data are the first to demonstrate that a homolog of mammalian PrRP (fish RFa) is a major hypothalamic peptide of PRL release in teleost fish.

Amino Acid Sequence↗

Synthesis of alpha-thiophenylglycine peptides. Novel peptide substrates useful in the study of microbial peptide transport.

The synthesis of peptides useful for the investigation of microbial peptide transport is reported. These peptides, L-alanyl-L-2-thiophenylglycine (Ala-alpha-TPG), L-alanyl-L-2-thiophenylglycyl-L-alanine (Ala-alpha-TPG-Ala) and L-alanyl-L-alanyl-L-2-thiophenylglycine (Ala-Ala-alpha-TPG), contain a phenylthio group attached to the alpha carbon of glycine.

Anti-Bacterial Agents↗

Comparison of the actions of bombesin, gastrin-releasing peptide-27, neuromedin B, and gastrin-releasing peptide-10 in causing release of gastrin and gastric inhibitory peptide in rats.

The objective of this study was to compare the gastrin- and gastric inhibitory peptide (GIP)-releasing actions of bombesin, gastrin-releasing peptide (GRP)-27, neuromedin B, and GRP-10 in rats. Both bombesin and GRP-27 are potent stimulants of gastrin and GIP release, whereas neuromedin B and GRP-10 are less effective, on a molar basis.

Animals↗

Site specificity of a catalytic vasoactive intestinal peptide antibody. An inhibitory vasoactive intestinal peptide subsequence distant from the scissile peptide bond.

Ten fragments of vasoactive intestinal peptide (VIP) were tested for reactivity with a human catalytic autoantibody that cleaves full-length VIP(1-28) at the Gln16-Met17 peptide bond. A large COOH-terminal subsequence, VIP(15-28), was bound by the autoantibody with high affinity (Ki 1.25 nM), suggesting that it is the antibody binding epitope. VIP(22-28), a short subsequence distant from the scissile bond, inhibited the binding (Ki 242 microM) and hydrolysis (Ki 260 microM) of full-length VIP by the catalytic autoantibody in a competitive fashion. The autoantibody did not show detectable binding of short VIP subsequences that encompass the scissile bond (VIP(15-21), VIP(11-17), and VIP(13-20]. These data show that residues 22-28, located four amino acids distant from the scissile bond, contribute in recognition of VIP by the catalytic autoantibody.

Amino Acid Sequence↗

Amino acids and peptides. LIII. Synthesis and biological activities of some pseudo-peptide analogs of PKSI-527, a plasma kallikrein selective inhibitor: the importance of the peptide backbone.

Pseudo-peptide analogs of trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-4-aminopheny l acetic acid (PKSI-527, plasma kallikrein selective inhibitor), in which an amide bond (peptide bond) has been replaced by a CH2-NH bond, i.e., trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (I), trans-4-aminomethylcyclohexanecarbonyl-psi (CH2-NH)-L-phenylalanyl-4-aminophenyl acetic acid (II) and trans-4-aminomethylcyclohexanecarbonyl-D-phenylalanyl-psi (CH2-NH)-4-aminophenyl acetic acid (III) were synthesized. These pseudo-peptide analogs did not exhibit any detectable inhibitory activity against plasma kallikrein (PK), plasmin (PL), urokinase (UK), thrombine (TH) or trypsin (TRY). These results indicate that both carbonyl groups in the PKSI-527 are important for the manifestation of potent inhibitory activity against plasma kallikrein.

Animals↗

Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction.

Brain natriuretic peptide (BNP), NT-proBNP and NT-pro-atrial natriuretic peptide (NT-proANP) were measured in blood samples from 57 patients using immunoassays and immunoradiometric assays to evaluate the usefulness as diagnostic markers for the detection of heart failure. For the detection of impaired left ventricular ejection fraction (LVEF), receiver operating characteristic curves showed that BNP had the best diagnostic performance with an area under curve (AUC) of 0.75+/-0.06. However, NT-proBNP (AUC: 0.67+/-0.07) and NT-proANP (AUC: 0.69+/-0.08) showed no significant difference to BNP. In a further analysis for the detection of resting LVEF <40%, BNP again was the best marker with an AUC of 0.83+/-0.06. NT-proBNP showed only a slightly smaller AUC (0.79+/-0.07). The AUC for NT-proANP was significantly smaller (0.65+/-0.08) compared to BNP. Additionally, BNP and NT-proBNP correlated negatively with the resting LVEF (BNP: -0.472, p<0.001; NT-proBNP: -0.306, p=0.026), whereas NT-proANP showed no significant correlation. In summary, BNP was the best marker to detect patients with impaired LVEF compared to NT-proBNP and NT-proANP. However, NT-proBNP showed no significant differences to BNP and it is therefore a new promising alternative marker for the detection of left ventricular dysfunction.

Aged↗