Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the development of bi-specific monoclonal antibodies (MAb) capable of simultaneous recognition of rabbit immunoglobulin G (IgG) and horseradish peroxidase (HRP) for use in a variety of immunobased techniques. This bi-specific antibody, named McC8, was produced by fusion of the aminopterin-sensitive mouse hybridoma MAP.Ag.1, which secretes MAb against HRP, and splenocytes from a mouse previously immunized with whole rabbit IgG. The resultant hybrid-hybridoma co-dominantly expresses and secretes the immunoglobulin chains, i.e., IgG1 and IgG2b, of its respective parents, as determined by radial immunodiffusion. The binding sites on rabbit IgG for McC8 were determined on Western blots and in competition solid-phase enzymatic immunoassays with the use of allotype-specific rabbit sera. Both these techniques demonstrated that McC8 recognizes the light chain of the rabbit IgG molecule with preferential binding to the B4 kappa light-chain allotype. McC8 was successfully used in two-step immunocytochemistry for localization of calcitonin gene-related peptide (CGRP) in fibers of the superficial layers of the spinal trigeminal nucleus of the rat, as well as for localization of glial fibrillary acidic protein (GFAP)-immunoreactive sites in primary rat septal cell cultures, thus demonstrating its potential as a general developing reagent in conventional immunocytochemistry. McC8 compared favorably with peroxidase-antiperoxidase immunocytochemistry with respect to sensitivity. However, the bi-specific developing reagent proved superior to the conventional peroxidase-antiperoxidase procedure when both were employed in a similar fashion in tissues prone to display high background staining. Finally, McC8 was also employed as a developing reagent in a competitive ELISA designed for quantitation of CGRP with the use of a rabbit anti-CGRP primary antibody. The sensitivity of this quantitative ELISA (190 pg or 50 fmol CGRP per well) renders this bi-specific antibody suitable for use in quantitative immunoassays for detection of relevant peptides in biological systems.
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PMID:Development of a bi-specific monoclonal antibody for simultaneous detection of rabbit IgG and horseradish peroxidase: use as a general reagent in immunocytochemistry and enzyme-linked immunosorbent assay. 229 80

Evidence has been accumulated implicating sex hormones as possible modulators of extrapyramidal motor function. In the present study we have investigated the effects of estrogens, progesterone, testosterone, prolactin and calcitonin on behavioral parameters related to nigro-striatal dopaminergic system, such as haloperidol-induced catalepsy in male rats. It was found that 7-days estradiol benzoate treatment (5 micrograms/rat/day) significantly increases haloperidol-induced catalepsy, suggesting a possible antidopaminergic activity of estrogens. On the other hand, prolactin facilitates nigro-striatal dopaminergic transmission. Interestingly, 7 day treatment with medroxy-acetate progesterone (MAP, 5 mg/Kg, i.p.) brings about a trend to a decrease in haloperidol-induced catalepsy, while no significantly effect was observed following acute MAP administration at the same dose. So, it is tempting to speculate that chronic progestinic treatment may result in an increase in dopaminergic tonus. Testosterone, acutely administered (5mg/kg.s.c.) induces changes similar to those observed following progesterone administration. Finally, also calcitonin is able to influence haloperidol-induced catalepsy by markedly increasing it.
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PMID:[Neuroendocrine modulation of haloperidol-induced catalepsy]. 630 68

Abnormal systemic and pulmonary vascular reactivity has been demonstrated in numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic pulmonary pressor response observed in these animals probably is responsible for the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We hypothesized that excess release of endogenous vasodilators such as calcitonin gene-related peptide (CGRP) in pneumonia was responsible for the diminished hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were instrumented for chronic hemodynamic monitoring and subsequently randomized to either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing 2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after the pneumonia or sham procedure and after the administration of 250 micrograms CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow was determined by the injection of radioactive microspheres. Forty-eight hours after the instillation of Pseudomonas, Pneumonia animals had significantly increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs. 118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR 0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were further characterized by increased mean pulmonary artery pressure (MPAP) as compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic variables and did not change the pressor response to hypoxia in either group. Furthermore, CGRP receptor blockade did not alter the distribution of blood flow in the lung during normoxia or hypoxia. These data suggest that although this model of acute pneumonia is characterized by an attenuated hypoxic pressor response, the mechanism does not appear to be mediated by excess release of the vasodilator CGRP.
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PMID:Calcitonin gene-related peptide does not mediate the abnormal vascular reactivity observed in a rat model of acute Pseudomonas pneumonia. 876 59

We have previously demonstrated that calcitonin gene-related peptide (CGRP) plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt) hypertension through an increase in vascular responsiveness to the dilator activity of this neuropeptide. Substance P (SP) is often co-localized with CGRP in perivascular sensory nerves. To determine the role and mechanism of action of SP in SN-salt hypertension, we induced hypertension in 4- to 6-week-old male Sprague-Dawley rats (n=8) by subtotal nephrectomy and 1% saline drinking water. Sham-operated rats were given either tap water (n=9) or 1% saline to drink (n=9). Eleven to 13 days after each protocol, all rats had intravenous (for drug administration) and arterial (for continuous monitoring of mean arterial pressure [MAP]) catheters surgically implanted and were studied in the conscious and unrestrained state. Baseline MAP was significantly elevated in the SN-salt rats (157 +/- 6 mm Hg) compared with tap water--fed controls (128 +/- 3 mm Hg) and 1% saline--fed controls (132 +/- 5 mm Hg). Vehicle administration did not alter the MAP in any group. In contrast, administration of spantide-II (0.2 micromol/L in saline), an SP receptor antagonist, significantly elevated the MAP in SN-salt rats (13.9 +/- 0.8 mm Hg) compared with the tap water (1.7 +/- 1.7 mm Hg) and 1% saline controls (2.0 +/- 1.9 mm Hg). SP mRNA and peptide levels in dorsal root ganglia were not significantly different between the 3 groups. Administration of exogenous SP (12 and 24 nmol center dot L(-1) center dot kg(-1) intravenously) resulted in a significantly greater decrease in MAP in the SN-salt rats compared with both control groups. Taken together, these data suggest that in SN-salt hypertension, SP plays a counterregulatory role in the absence of an increase in its neuronal expression, thereby suggesting that one possible mechanism of this compensatory vasodilator response is enhanced vascular reactivity to SP.
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PMID:Substance P in subtotal nephrectomy-salt hypertension. 1188 78

To determine the role of endothelin-1 (ET-1) and its receptors in the regulation of calcitonin gene-related peptide (CGRP) release, male Wistar rats were divided into six groups and subjected to the following treatments for 1 wk with or without ABT-627 (an ET(A) receptor antagonist, 5 mg.kg(-1).day(-1) in drinking water) or A-192621 (an ET(B)-receptor antagonist, 30 mg.kg(-1).day(-1) by oral gavage): control (Con), ET-1 (5 ng.kg(-1).min(-1) iv), Con + ABT-627, Con + A-192621, ET-1 + ABT-627, and ET-1 + A-192621. Baseline mean arterial pressure (MAP, mmHg) was higher (P < 0.05) in Con + A-192621 (122 +/- 4) and ET-1 + A-192621 (119 +/- 4) groups compared with Con (104 +/- 6), ET1 (106 +/- 3), Con + ABT-627 (104 +/- 3), and ET1 + ABT-627 (100 +/- 3) groups. Intravenous administration of CGRP(8-37) (a CGRP receptor antagonist, 1 mg/kg) increased MAP (P < 0.05) in ET-1 (13 +/- 1), Con + A-192621 (12 +/- 1), and ET-1 + A-192621 (15 +/- 3) groups compared with Con (4 +/- 1), Con-ABT-627 (4 +/- 1), and ET-1 + ABT-627 (5 +/- 1) groups. Plasma CGRP levels (in pg/ml) were increased (P < 0.05) in ET-1 (57.5 +/- 6.1), Con + A-192621 (53.9 +/- 3.4), and ET-1 + A-192621 (60.4 +/- 3.0) groups compared with Con (40.4 +/- 1.6), Con + ABT-627 (40.0 +/- 2.9), and ET-1 + ABT-627 (42.6 +/- 1.9) groups. Plasma ET-1 levels (in pg/ml) were higher (P < 0.05) in ET-1 (2.8 +/- 0.2), ET-1 + ABT-627 (3.2 +/- 0.4), Con + A-192621 (3.3 +/- 0.4), and ET-1 + A-192621 (4.6 +/- 0.3) groups compared with Con (1.1 +/- 0.2) and Con-ABT-627 (1.3 +/- 0.2) groups. Therefore, our data show that ET-1 infusion leads to increased CGRP release via activation of the ET(A) receptor, which plays a compensatory role in preventing ET-1-induced elevation in blood pressure.
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PMID:Prevention of endothelin-1-induced increases in blood pressure: role of endogenous CGRP. 1520 72

The product of FeSOD activity is hydrogen peroxide (H2O2). Furthermore, FeSOD can modify the chemical versatility of NO into its redox-active forms: nitrosonium cation (NO+) and nitroxyl anion (NO-). All of these low molecular weight species are vasoactive and, in particular, NO- induces calcitonin gene-related peptide (CGRP) synthesis (known to be the most potent relaxation-promoting peptide). In this study the effects of bolus infusions of iron-containing superoxide dismutase (FeSOD) and of superoxide dismutase containing both iron and manganese (FeMnSOD) on the arterial blood pressure (MAP), the arterial blood pressure (CO) and the total vascular resistance (TVR) in spontaneously hypertensive (SH) rats were determined. Bolus infusion of FeSOD induced a biphasic response in the MAP (an initial increase was followed by a significant decrease). At the end of the experiment the MAP returned to its basal value. FeMnSOD (the enzymatically inactive form of FeSOD) had no effect on the MAP in these experiments. Bolus infusions of FeSOD and of FeMnSOD had no effect either on the both the CO or on the TVR in SH rats. Our results indicate that arterial relaxation changes mediated by NO- may be important for regulation of blood pressure in SH rats.
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PMID:The effects of iron-containing superoxide dismutases on haemodynamic parameters in spontaneously hypertensive rats. 1719 60

This study was designed to examine the role of the endocannabinoids in blood pressure regulation during high sodium (HS) intake. HS (4% Na+ by weight) intake for 3 weeks increased baseline mean arterial pressure (MAP, mm Hg) compared with normal sodium (NS, 0.4% Na+ by weight)-treated male Wistar rats. Capsazepine (3 mg/kg), a selective transient receptor potential vanilloid type 1 (TRPV1) antagonist, caused a greater increase in MAP (mm Hg) in HS-treated compared with NS-treated rats (13+/-3 versus 4+/-2, p<0.05), whereas calcitonin gene-related peptide (CGRP) dose-dependently decreased MAP in both HS- and NS-treated rats with a more profound effect in the former. HS increased plasma anandamide levels analyzed by liquid chromatography/electrospray tandem mass spectrometry (NS, 2.40+/-0.31 versus HS, 4.05+/-0.47 pmol/ml, p<0.05) and plasma CGRP levels determined by radioimmunoassay (NS, 36.6+/-3.8 versus HS, 55.7+/-6.4 pg/ml, p<0.05). Methanandamide, a metabolically stable analog of anandamide, caused a greater CGRP release in mesenteric arteries isolated from HS-treated compared with NS-treated rats. Western blot showed that expression of receptor activity-modifying protein 1, a subunit of the CGRP receptor, in mesenteric arteries was greater in HS-treated compared with NS-treated rats. These results show that HS intake increases production of anandamide, which may serve as an endovanilloid to activate TRPV1, leading to release of CGRP to blunt salt-induced increases in blood pressure. These data support the notion that TRPV1 may act as a molecular target for salt-induced elevation of endovanilloid compounds to regulate blood pressure.
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PMID:Endocannabinoid regulates blood pressure via activation of the transient receptor potential vanilloid type 1 in Wistar rats fed a high-salt diet. 1730 41

Calcitonin gene-related peptide is a 37 amino acid neuropeptide. Although calcitonin gene-related peptide activates a G-protein-coupled receptor, recent evidence suggests that calcitonin gene-related peptide induces more complex signaling cascades including the activation of MAP kinases [Eur J Pharmacol; 389:125-130 (2000), Neuropeptides; 34:229-233 (2000)]. However, the molecular mechanisms of this activation still remain to be elucidated. For the first time we applied a proteomics approach in order to identify molecular targets of calcitonin gene-related peptide downstream signaling in the neuroblastoma cell line SK-N-MC and identified proteins that changed either their expression, location, or their post-translational modifications in a time-dependent manner after calcitonin gene-related peptide stimulation.
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PMID:Proliferative effect of calcitonin gene-related peptide is induced by at least five proteins as identified by proteome profiling. 1731 53

Activation of trigeminal nerves and release of neuropeptides that promote inflammation are implicated in the underlying pathology of migraine and temporomandibular joint (TMJ) disorders. The overall response of trigeminal nerves to peripheral inflammatory stimuli involves a balance between enzymes that promote inflammation, kinases, and those that restore homeostasis, phosphatases. The goal of this study was to determine the effects of a cocoa-enriched diet on the expression of key inflammatory proteins in trigeminal ganglion neurons under basal and inflammatory conditions. Rats were fed a control diet or an isocaloric diet enriched in cocoa for 14days prior to an injection of noxious stimuli to cause acute or chronic excitation of trigeminal neurons. In animals fed a cocoa-enriched diet, basal levels of the mitogen-activated kinase (MAP) phosphatases MKP-1 and MKP-3 were elevated in neurons. Importantly, the stimulatory effects of acute or chronic peripheral inflammation on neuronal expression of the MAPK p38 and extracellular signal-regulated kinases (ERK) were significantly repressed in response to cocoa. Similarly, dietary cocoa significantly suppressed basal neuronal expression of calcitonin gene-related peptide (CGRP) as well as stimulated levels of the inducible form of nitric oxide synthase (iNOS), proteins implicated in the underlying pathology of migraine and TMJ disorders. To our knowledge, this is the first evidence that a dietary supplement can cause upregulation of MKP, and that cocoa can prevent inflammatory responses in trigeminal ganglion neurons. Furthermore, our data provide evidence that cocoa contains biologically active compounds that would be beneficial in the treatment of migraine and TMJ disorders.
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PMID:Cocoa-enriched diets enhance expression of phosphatases and decrease expression of inflammatory molecules in trigeminal ganglion neurons. 2013 52