The effect of massage on patients with chronic fatigue syndrome: A systematic review and meta-analysis.

BACKGROUND: Chronic fatigue syndrome (CFS) is a long-term and complex chronic disease that seriously affects the physical and mental health and quality of life of patients. Massage, as one of the methods in traditional Chinese medicine, can treat both symptoms and root causes and is widely used to treat CFS. The main purpose is to systematically evaluate the impact of massage therapy on the efficacy and safety of CFS patients, providing a reference for clinical practice. METHODS: By searching for literature published in PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, VIP Database, and China National Knowledge Infrastructure Database until November 2023, randomized controlled trial studies were selected according to the established inclusion and exclusion criteria. The Cochrane system evaluation manual was used to evaluate the quality of the included studies, and RevMan5.4 software was used for meta-analysis. RESULTS: 32 randomized controlled trials were included, with a total of 2594 CFS patients. Meta-analysis showed that the total score of the fatigue scale (FS-14) in the treatment group, MD = -1.59, 95% CI (-1.84, -1.34), P < .00001; Physical fatigue score, MD = -1.30, 95% CI (-1.60, -1.00), P < .00001; Mental fatigue score, MD = -0.84, 95% CI (-0.99, -0.72), P < .0001]; Effective rate [RR = 1.23, 95% CI (1.19,1.28), P < .00001]; all indicators were superior to the control group, Only one study reported adverse reactions, including local swelling, skin bruising, and nausea. CONCLUSION: Our research findings suggest that massage therapy has a significant therapeutic effect on CFS, avoiding adverse reactions and improving fatigue symptoms. Therefore, massage therapy for chronic fatigue syndrome should be further promoted and applied.

Synthesis and Anticonvulsant Activity of 3-(alkylamino, alkoxy)-1,3,4,5- Tetrahydro-2H-benzo [b] azepine-2-one Derivatives.

BACKGROUND & OBJECTIVE: A series of novel 3-Substituted-1,3,4,5-Tetrahydro-2H-benzo [b] azepine-2-one Derivatives (4, 5, 7, 10, 12, 5a-j, 8a-e) were synthesized from 1,2,3,4-Tetrahydro-1- naphthalenone. The structures of these compounds were confirmed by IR, 1H NMR, 13C NMR, MASS spectra and elemental analysis. Their anticonvulsant activity was evaluated by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. Compound 4 showed the maximum anticonvulsant activity against the maximal electroshock test (ED50=26.4, PI =3.2) and against the subcutaneous pentylenetetrazol test (ED50=40.2, PI =2.1). CONCLUSION: Possible structure-activity relationship was discussed.

Mesenchymal stem cells-conditioned medium protects PC12 cells against 2,5-hexanedione-induced apoptosis via inhibiting mitochondria-dependent caspase 3 pathway.

Studies suggested that the conditioned medium of mesenchymal stem cells (MSC-CM) inhibited the increased apoptosis in various cells. However, there are no reports underlying the protection of MSC-CM against 2,5-hexanedione (HD)-induced apoptosis in neural cells. In the present study, the viability was observed in PC12 cells that received HD alone or with MSC-CM by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was estimated by Hoechst 33342 staining and flow cytometry. Mitochondrial transmembrane potential was examined by rhodamine 123. Moreover, we investigated the expression of Bax and Bcl-2, cytochrome c translocation, and caspase 3 activity by real-time polymerase chain reaction, Western blot, and immunochemistry. Nerve growth factor (NGF) was examined in MSCs and MSC-CM. Our results showed that MSC-CM promoted cell survival and reduced apoptosis in HD-exposed PC12 cells. Moreover, MSC-CM significantly reversed disturbance of Bax and Bcl-2, ameliorated disruption of mitochondrial transmembrane potential, and reduced release of cytochrome c and activity of caspase 3 in HD-exposed PC12 cells. In the meantime, NGF was detected in MSCs and MSC-CM. These findings demonstrate that MSC-CM protects against HD-induced apoptosis in PC12 cells via inhibiting mitochondrial pathway. Our results indicate that NGF in MSC-CM may be involved in the protection of MSC-CM against HD-induced apoptosis. Our study clarifies the protection of MSC-CM on HD neurotoxicity and its underlying mechanism.

Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3-a]azepines as Anticonvulsant Agents.

A series of new 8-alkylamino-5, 6-dihydro-4H-benzo[f][1,2,4]triazolo [4,3-a]azepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. The results of these tests showed that 8-heptylamino-5,6- dihydro-4H-benzo[f][1,2,4] triazolo[4,3-a]azepine (7g) was the most promising compound, with median effective dose (ED50) of 19.0 mg/kg, and protective index (PI) value of 14.8 in the MES test, which is much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin (PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The possible structure-activity relationship was discussed.

[Screening the proteins of organophosphoms ester-induced delayed neurotoxicity in the cerebral tissue of hens exposed to tri-ortho-cresyl phosphate].

OBJECTIVE: To screen the proteins with differential expression levels in the cerebral tissue of hens exposed to tri-ortho-cresyl phosphate (TOCP), and to provide target proteins for studying the mechanism of organophosphoms ester-induced delayed neurotoxicity (OPIDN). METHODS: Thirty two adult Roman hens were randomly divided into four groups: TOCP group was exposed to 1000 mg/kg TOCP, PMSF group was exposed to 40 mg/kg PMSF, PMSF plus TOCP group was exposed to 40 mg/kg PMSF and after 24 h exposed to 1000 mg/kg TOCP, control group was exposed to normal saline. All hens exposed to chemicals by gastro-intestine for 5 days were sacrificed, and the cerebral tissue were dissected and homogenized in ice bath. Total proteins extracted from the cerebral tissue were separated by isoelectric focusing as the first dimension and SDS-PAGE as the second dimension. The 2-DE maps were visualized after silver staining and analyzed by Image Master 2D software. At last ,the expressed protein spots were identified by Mass spectrometry. RESULTS: From total proteins in TOCP group, the PMSF plus TOCP group and PMSF group, 1185, 1294 and 1063 spots were detected, respectively. One thousand three hundred thirty two spots from total proteins in control group were detected. The match rates of protein spots in TOCP group, the PMSF plus TOCP group and PMSF group were 78.32 %, 79.56 % and 80.93%, respectively. There were 235 protein spots with differential expression levels between TOCP group and control group, which included 158 up regulation spots and 77 down regulation spots. According to the PMSF features, there were 102 spots with differential expression levels between TOCP group and control group and without differential expression levels between TOCP group and PMSF plus TOCP group, among them there were 13 spots with 4 fold differential expression levels between TOCP group and control group and without differential expression levels between TOCP group and PMSF group. Seven protein spots (homer-1b, Destrin, heat shock protein 70, eukaryotic translation initiation factors, proteasome alpha1 subunit, lactate dehydrogenase B, glutamine synthetase) were detected by Mass spectrometry. CONCLUSION: There are 112 protein spots with differential expression levels of the cerebral tissue in TOCP group, which may be related to OPIDN, among them 13 protein spots with differential expression levels are associated closely with OPIDN. Seven protein spots detected by Mass spectrometry may be related to the mechanism induced by OPIDN.

9-(2-Chloro-benz-yloxy)-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3(5H)-one.

In the title mol-ecule, C(18)H(16)ClN(3)O(2), the seven-membered ring adopts an envelope conformation with the flap atom deviating by 0.801 (5) Šfrom the mean plane formed by the remaining non-H atoms. Inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. The crystal packing also exhibits weak inter-molecular C-H⋯N hydrogen bonds and π-π inter-actions with a short distance of 3.734 (3) Šbetween the centroids of the aromatic rings of neighbouring mol-ecules.

Decrease in birth weight and gestational age by arsenic among the newborn in Shanghai, China.

OBJECTIVES: To assess the effects of trace metals on birth weight and gestational age among newborn babies of mothers without occupational exposure. METHODS: The subjects examined were 142 newborn babies (71 males and 71 females) delivered at two university hospitals in Shanghai, China and their parents. Relationships of newborn birth weight and gestational age to concentrations of arsenic, lead, cadmium, manganese, zinc, and cobalt in maternal and cord blood were investigated. RESULTS: Birth weight was 3379.5 +/- 440.8 (2090-4465) g and the gestational age was 39.7 +/- 1.3 (35-43) weeks. Stepwise regression analysis indicated that, in the male newborn, birth weight and gestational age were inversely related to the logarithm arsenic concentration (4.13 +/- 3.21 microg/l) in mothers' whole blood. CONCLUSION: Arsenic might have a negative influence on newborn birth weight and gestational age at a relatively low exposure level. This effect was observed in male but not female babies, suggesting a sex differential in susceptibility to arsenic at an early stage of development. Although birth weight is believed to be related to gestational age, arsenic may directly affect both birth weight and gestational age.

Synthesis and anticonvulsant activity of 8-alkoxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one derivatives.

A series of novel 8-alkoxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The results of these tests demonstrated that 8-heptyloxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one (3f) and 8-hexyloxy -5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one (3e) were the most promising compounds, with median effective dose (ED(50)) of 17.6 and 17.9 mg/kg, and protective index (PI) of greater than 63.4 and 62.4 in the MES test, respectively. These PI values were higher than the PI value of the prototype antiepileptic drug carbamazepine. The scPTZ test showed that 8-pentyloxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-one (3d) was the most potent with ED(50) value of 38.0 mg/kg and PI value of greater than 29.4, which is much safer than marketed drug carbamazepine. The possible structure-activity relationship was discussed.

[The differential expression of Stathmin in the spinal cord tissue of hens exposed to tri-o-cresyl phosphate].

OBJECTIVE: To screen the differently expressed proteins related to regulating the depolymerization of microtubules in the spinal cord of hens exposed to tri-o-cresyl phosphate (TOCP) and to provide target protein evidence for exploring the mechanisms of the delayed neurotoxicology (OPIDN) induced by organophosphorus compounds (OPs). METHODS: Forty two Roman hens were randomly divided into three groups, i.e. TOCP group treated with 1000 mg/kg TOCP; intervention group treated with 40 mg/kg phenylmethanesulfonyl fluoride (PMSF) before 1000 mg/kg TOCP treatment and control group treated with tap water. Four hens in each group were sacrificed on the 5th and 20th days after exposure, respectively. Spinal cords were separated and homogenates at low temperature, and the total proteins were extracted. The OPIDN symptoms observed and recorded in the remaining 6 hens in each group. The differently expressed proteins related to regulating the depolymerization of microtubules were screen by two-dimensional electrophoresis and mass spectroscopy (MS). RESULTS: The OPIDN symptoms appeared on the 5th day after exposure in TOCP group, which were gradually serious with time. The results by two-dimensional electrophoresis and MS showed that the Stathmin expression was downregulated 3.4 times and 2.8 times in TOCP group, respectively, as compared with the control and PMSF intervention groups. However, there was no significant difference of the Stathmin expression between control group and PMSF intervention group. CONCLUSION: The Stathmin expression in the spinal cord tissues of hens exposed to TOCP significantly downregulated. Moreover, the downregulated Stathmin expression may be related to excess polymerization of microtubules and the mechanism of OPIDN.

(1E)-6-Meth-oxy-3,4-dihydro-naphthalen-1(2H)-one oxime.

In the crystal structure of the title compound, C(11)H(13)NO(2), the mol-ecules are paired into centrosymmetric dimers via inter-molecular O-H⋯N hydrogen bonds.

Maternal and fetal exposure to four carcinogenic environmental metals.

OBJECTIVE: To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences. METHODS: Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Environmental factors that might play a role in exposure were analyzed using Mann-Whitney nonparametric U-tests and multiple linear regression. RESULTS: The concentrations of As, Cd, and Ni in umbilical cord blood (5.41, 0.87, and 139.54 µg/L) were significantly lower than those in maternal blood (6.91, 1.93, and 165.93 µg/L). There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that: (i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; (ii) living close to major transportation routes (<500 m) or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and (iii) living close to industrial chimneys induced high maternal Ni levels. Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens. CONCLUSION: Both mothers and fetuses had been exposed to As, Cd, Ni, and Be. The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors, such as occupational exposure, contact with second-hand smoke and living close to major transportation routes or industrial chimneys.

(1E)-6-Meth-oxy-3,4-dihydro-naphthalen-1(2H)-one O-(p-tolyl-sulfon-yl)oxime.

In the title compound, C(18)H(19)NO(4)S, the two benzene rings form a dihedral angle of 68.37 (11)°. One of the C atoms of the fused ring bonded to the N atom displays positional disorder with site-occupation factors of 0.763 (7) and 0.237 (7) and the ring has an envelope conformation with the disordered C atoms located on opposite sides of the plane formed by the other atoms. In the crystal, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules to form a two-dimensional supra-molecular network. The crystal structure is further stablized by weak inter-molecular C-H⋯π inter-actions.

Different regulation of atrial ANP release through neuropeptide Y2 and Y4 receptors.

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y(4) receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y(4) receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y(2) receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y(1, 2, 5) receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y(3) receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y(2) receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y(4) and Y(2) receptor differently regulate the release of atrial ANP.

Ribavirin and IFN-alpha combination therapy induces CD4+ T-cell proliferation and Th1 cytokine secretion in patients with chronic hepatitis B.

AIM: To investigate the anti-viral mechanism of combination therapy of interferon (IFN)-alpha and ribavirin in patients with chronic hepatitis B. METHODS: Twenty patients were assigned to receive either IFN-alpha plus ribavirin (group A, n = 14) or no treatment as a control (group B, n = 6). Patients were analyzed for T-cell proliferative responses specific for hepatitis B virus (HBV)-antigen and cytokine production by peripheral blood mononuclear cells (PBMCs). RESULTS: Combination therapy induced HBV-antigen specific CD4+ T-cell proliferative responses in four patients (28.6%). Production of high levels of HBV-specific IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 by PBMCs was found in five patients (35.7%), who showed significantly lower HBV DNA levels in serum at 12 mo after treatment ended (P = 0.038) and at 24 mo of follow-up (P = 0.004) than those without high levels of cytokine production. CONCLUSION: HBV-antigen specific CD4+ T cells may directly control HBV replication and secretion of anti-viral T helper 1 (Th1) cytokines by PBMCs during combination therapy of chronic hepatitis B with ribavirin and IFN-alpha.

[Effects of sodium arsenite on catalase in human keratinocytes].

OBJECTIVE: To evaluate the effects of sodium arsenite on the activity, the mRNA and the protein expression of CAT in human keratinocyte cell line (HaCaT). METHODS: The activity of catalase (CAT) was detected by ultraviolet direct velocity assay. RT-PCR was used to detect the mRNA expression of CAT and Western blotting was conducted to detect the protein expression of CAT. RESULTS: If the cells were treated with higher than 5.0 micromol/L sodium arsenite, the activity, mRNA and protein expression of CAT were decreased significantly and in a dosage dependent fashion (P < 0.05). CONCLUSION: CAT is inhibited by sodium arsenite in the transcription, translation and activity levels.

Augmentation of insulin-stimulated ANP release through tyrosine kinase and PI 3-kinase in diabetic rats.

The aim of present study was to define the effects of insulin on atrial dynamics and ANP release and its modification in diabetic rats. An isolated perfused beating atrial model was used from control and diabetic rats. Insulin was perfused with and without an inhibitor for tyrosine kinase or phosphatidylinositol 3-kinase (PI 3-kinase). Insulin increased the release of ANP and decreased atrial contractility in a dose-dependent manner. During the perfusion of 10(-10)M insulin, the release of ANP abruptly increased within 8min by approximately 40% and then decreased with time despite of continuous perfusion. In terms of increasing the dose of insulin, the time to reach the peak effect became faster and the slope to decrease became slower. In contrast, atrial contractility was gradually decreased with time. These effects were independent upon extracellular glucose. Genistein (10(-5)M) or lavendustin C (10(-5)M), a tyrosine kinase inhibitor, attenuated the release of ANP stimulated by insulin (10(-8)M). Wortmannin (10(-7)M) or LY294002 (10(-5)M), a PI 3-kinase inhibitor, also attenuated insulin-stimulated ANP release. However, both inhibitors for PI 3-kinase and tyrosine kinase did not cause any significant effects on negative inotropism by insulin. Insulin-stimulated ANP release was augmented in streptozotocin-treated rat atria. The density of insulin receptor markedly increased in diabetic hearts. These results suggest that insulin stimulates the release of ANP through PI 3-kinase and tyrosine kinase, and augmentation of insulin-stimulated ANP release in diabetic rat atria may be partly due to an upregulation of insulin receptor.

ATP-stimulated ANP release through P1 receptor subtype.

Extracellular ATP acts as a local regulator of physiological functions in the cardiovascular system via P1 and P2 receptors. However, little is known about the effect of ATP on the release of atrial natriuretic peptide (ANP) secretion. The purpose of this study was to investigate the effects of extracellular ATP on atrial hemodynamics and ANP release and to identify their receptor-mediated mechanism. ATP was infused into isolated perfused beating rat atria in the absence and presence of various receptor antagonists. ATP (from 0.1 to 30 microM) increased the ANP release with negative inotropism in a dose-dependent manner. ADP (30 microM) also caused an increase in ANP release with similarity to ATP, but alpha,beta-methylene ATP (alpha,beta-MeATP, P2X1 receptor agonist) and 2-methylthioADP (2-MesADP, P2Y1 receptor agonist) did not. The rank order of potency for the increment of ANP release was adenosine>ATP=ADP>2-MesADP>alpha,beta-MeATP. In contrast, UTP, an agonist for P2Y2,4,6 receptor, caused a decrease in ANP release without changes in contractility. Extracellular ATP-induced increase in ANP release and negative inotropism were completely blocked by the pretreatment of 8-cyclopentyl-1,3-dipropylxanthine (P1 receptor antagonist), but not by pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid (P2X1 receptor antagonist) and suramin (P2XY receptor antagonist). Reactive Blue 2 (P2Y receptor antagonist) caused an augmentation of ATP-induced increase in ANP release without affecting negative inotropism. Adenosine 5'-(alpha,beta-methylene) diphosphate, an ectonucleotidase inhibitor, did not affect ATP-induced augmentation of ANP release with negative inotropy. These results suggest that extracellular ATP-induced increase in ANP release and negative inotropism are mediated mainly by P1 receptor, and UTP decreases ANP release. Therefore, we suggest that extracellular ATP and UTP may have opposite actions on the regulation of ANP secretion.

Dendroaspis natriuretic peptide and its functions in pig ovarian granulosa cells.

Dendroaspis natriuretic peptide (DNP), a 38-amino acid peptide, was isolated from the venom of green mamba. It has structural and functional similarities to the other members of the natriuretic peptide family. The purpose of this study was to determine whether DNP is present in pig ovarian granulosa cells and to define its biological functions. The serial dilution curves of extracts of granulosa cells and follicular fluid were parallel to the standard curve of DNP, and a major peak of molecular profile of both extracts by HPLC was synthetic DNP. The concentration of DNP was 7.51+/-1.46 pg/10(7) cells and 24.81+/-2.38 pg/ml in granulosa cells and follicular fluid, respectively. Natriuretic peptides increased cGMP production in the purified membrane of granulosa cells with a rank order of potency of C-type natriuretic peptide (CNP)>atrial natriuretic peptide (ANP)=DNP. mRNAs for natriuretic peptide receptor-A (NPR-A), NPR-B and NPR-C were detected by RT-PCR. The binding site of (125)I-DNP was also observed in granulosa cell layer by in vitro autoradiography. Synthetic DNP inhibited the secretion of ANP from granulosa cells in a concentration-dependent manner and the potency was similar to CNP. The concentration of DNP and CNP, which inhibited the secretion of ANP by 50%, was about 1 nM. Increases in production of cGMP in granulosa cells were observed by DNP or CNP. Therefore, these results show the existence of DNP system and the cross-talk between natriuretic peptides in pig ovarian granulosa cells.

Amylin-induced suppression of ANP secretion through receptors for CGRP1 and salmon calcitonin.

Amylin cosecretes with insulin from pancreatic beta-cells and shows high sequence homology with CGRP, adrenomedullin, and salmon calcitonin. This study aimed to investigate the effect of amylin on the atrial hemodynamics and ANP release from rat atria and to identify its receptor subtypes. Isolated perfused left atria from either control or streptozotocin-treated rats were paced at 1.3 Hz. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [3H]-inulin clearance. Rat amylin increased atrial contractility and suppressed the release of ANP. Rat CGRP showed similar effects but was approximately 300-fold more potent than amylin. Pretreatment with receptor antagonist for CGRP1 [rat alpha-CGRP (8-37)] or salmon calcitonin [acetyl-(Asn30, Tyr32)-calcitonin(8-32), (AC 187)] blocked the suppressive effect of ANP release and the positive inotropic effect by rat amylin. However, receptor antagonists for amylin [amylin (8-37), acetyl-amylin] did not block those effects. Amylin (8-37), acetyl-amylin, or rat alpha-CGRP (8-37) alone accentuated the release of ANP with no changes in atrial contractility. The effect of rat amylin and rat amylin (8-37) on the ANP release was attenuated in streptozotocin-treated rats. We suggest that amylin suppressed ANP release with increased atrial contractility through receptors for CGRP1 and salmon calcitonin and the attenuation of amylin and its antagonist on ANP release from streptozotocin-treated rat atria may be due to the downregulation of amylin receptor.

Calcitonin gene-related peptide-induced suppression of atrial natriuretic peptide release through receptors for CGRP1 but not for calcitonin and amylin.

Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is found in the central nervous system as well as in the heart. CGRP shows high sequence homology with amylin, salmon calcitonin, and adrenomedullin. This study aimed to investigate the effect of CGRP on atrial hemodynamics and atrial natriuretic peptide (ANP) release by using isolated perfused beating left atria and to identify its receptor subtypes. Rat alpha-CGRP (0.1, 1, 10, or 100 nM) increased atrial contractility and suppressed the release of ANP in a concentration-dependent manner. However, cys-CGRP (1 microM), a CGRP(2) receptor agonist, slightly decreased ANP release without positive inotropism. Human alpha-CGRP (1 nM) showed an effect on ANP release similar to that of rat alpha-CGRP with potent positive inotropism. However, salmon and rat calcitonin (1 microM) caused a slight decrease or no change in ANP release. Pretreatment with a receptor antagonist for CGRP(1) [rat alpha-CGRP-(8-37)] blocked rat alpha-CGRP-induced suppression of ANP release and positive inotropism, whereas the antagonists for salmon or amylin did not. Therefore, we suggest that rat alpha-CGRP causes a suppression of ANP release with positive inotropism through the receptor for CGRP(1) but not that for calcitonin and amylin.