Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms underlying the severe urinary retention induced by acrylamide intoxication were studied in detail in the rat. Subcutaneous treatment with acrylamide monomer (50 mg/kg daily for 10 days) almost completely impaired the micturition reflex, resulting in urinary retention. In fact, the ability to eliminate an oral water load was virtually abolished, while bladder filling with saline (transvesical cystometrogram) failed to activate reflex micturition. Instead, a picture of overflow incontinence resulted in urethane-anaesthetized rats, which was not reversed by intravenous administration of 4-aminopyridine. The nerve-mediated contractile response to field stimulation (0.1-20 Hz, 0.5 ms, 60 V) of the isolated bladder was unaffected, thus suggesting the integrity of bladder efferent innervation, and no evidence was found from in vitro experiments that the myogenic contractility of the bladder was depressed by acrylamide treatment. Conversely, the sensory nerve-mediated response to capsaicin was abolished and sensory nerve fibres of the bladder were selectively depleted of their content of substance P- and calcitonin gene-related peptide immunoreactivity following acrylamide treatment. In fact, concentrations of the same neuropeptides in other organs, including the adjoining ureters, were unaffected. As to the urethral segment, including the striated sphincter, the D-tubocurarine (0.2 mM)-sensitive urethral response to electrical stimulation (0.1 Hz, 0.1 ms, 20 V) was significantly reduced in acrylamide-treated animals. At the same level, neurofilament protein immunostaining revealed striking accumulations of neurofilament protein-like material in motor end-plates, thus indicating that neuromuscular junctions of the urethral striated sphincter were severely affected. Thus, the afferent arm of the micturition reflex was shown to be severely deranged by acrylamide intoxication, especially in its capsaicin-sensitive component. Since twitch-like contractions of the urethral striated sphincter are probably involved in promoting bladder voiding, a decreased efficiency of this mechanism could participate in the picture of urinary retention induced by acrylamide.
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PMID:Acrylamide-induced visceral neuropathy: evidence for the involvement of capsaicin-sensitive nerves of the rat urinary bladder. 164 5

Since the growth hormone-releasing peptide (GHRP), His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, was found to specifically release growth hormone by a complementary but yet not clearly defined action on the pituitary as well as the hypothalamus, in vitro studies have been performed to demonstrate and characterized GHRP binding sites on peripheral membranes of both the rat anterior pituitary and hypothalamus. Optimum binding assay conditions were established using [125I]Tyr-Ala-GHRP as the radioligand. The membrane binding sites were specific, reversible, saturable and time, temperature, pH and concentration dependent. Computerized analyses of competition experiments suggested two classes of binding sites in both pituitary and hypothalamic membranes. The maximum specific binding was observed at pH 5.0 than the physiological pH in both tissues. Pretreatment of the membranes with trypsin prevented specific binding. The increase in Bmax was statistically significant and showed a 2.0- to 8.9-fold and 5.8- to 11.2-fold in pituitary and hypothalamus, respectively, whereas the affinity constants (Kds) were not significant. Of the synthetic and natural neuropeptides that influence the release of GH from somatotrophs, only (D-Lys3)GHRP, substance P antagonists and growth hormone-releasing factor analog were potent inhibitors of GHRP binding in both tissues.
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PMID:Demonstration and characterization of the specific binding of growth hormone-releasing peptide to rat anterior pituitary and hypothalamic membranes. 171 88

The effect of acrylamide intoxication on the innervation and local control of the rabbit central ear artery was investigated. There was no difference in the noradrenaline, neuropeptide Y and calcitonin gene-related peptide tissue content between control and experimental animals. There was, however, a slight reduction in catecholamine histofluorescence. Although the contractile efficiency of the rabbit central ear artery as measured by responses to potassium chloride was unchanged, nerve-mediated contractile responses were significantly attenuated in acrylamide-treated animals. Contractile responses induced by exogenous alpha,beta-methylene ATP were markedly increased after acrylamide treatment, in contrast to contractions induced by exogenous noradrenaline which were attenuated at maximal concentrations. Modulatory effects of nerve-mediated contractile responses by neuropeptide Y were unaffected by acrylamide intoxication. It therefore appears that acrylamide intoxication damages sympathetic cotransmission, perhaps with preferential action on the purinergic component. Endothelium-dependent relaxant responses to acetylcholine and substance P were attenuated in acrylamide-treated animals, whereas relaxant responses mediated by calcitonin gene-related peptide (endothelium independent) were unaffected. The question of whether the damage to the endothelial cell action is a primary effect, or a secondary consequence of sympathetic nerve damage, is discussed.
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PMID:Changes in sympathetic and endothelium-mediated responses in the rabbit central ear artery after acrylamide treatment. 175 64

The effects of chronic acrylamide treatment on the autonomic nervous system were investigated by histochemical and pharmacological studies. Histochemical studies showed that acrylamide caused different degrees of damage to different nerve fibre types: calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerves showed the greatest reduction in intensity and number; noradrenaline (NA)-containing nerves were somewhat less affected; substance P (SP)-IR nerves were reduced in number, but this was not significant. The profiles of SP- and particularly of CGRP-IR nerves from treated animals were noticeably different to those from the control group, being flattened and irregular. Periarterial nerve stimulation (4-32 Hz) of the isolated rat mesenteric arterial bed preparation at basal tone elicited frequency-dependent vasoconstrictor responses. The magnitude of these responses was significantly reduced at higher frequencies in acrylamide-treated animals. In preparations with tone raised by the addition of methoxamine (10(-5) M), and in the presence of guanethidine (5 x 10(-6) M), periarterial nerve stimulation elicited vasodilator responses. These responses, which result from stimulation of sensory nerves, were greatly reduced in acrylamide-treated animals. There was a tendency for mesenteric beds from acrylamide-treated animals to show increased vasoconstrictor responses to doses of exogenous NA, although this was not significant. Responses to exogenous adenosine 5'-triphosphate (a cotransmitter with NA from sympathetic nerves) were not affected. In the raised-tone preparation, vasodilator responses to exogenous CGRP (the principal vasodilator sensory transmitter of rat mesenteric arteries) were not affected by acrylamide treatment. Hence, it is unlikely that the reduced responses to nerve stimulation were due to defects in the postjunctional receptors for the principal transmitters of sympathetic and sensory-motor nerves. There was no difference in the ability of mesenteric beds from control and treated animals to vasodilate in response to acetylcholine or sodium nitroprusside, or to vasoconstrict in response to potassium chloride, indicating normal smooth muscle and endothelial responses. These results suggest that chronic acrylamide treatment produces peripheral autonomic neuropathy of rat mesenteric vessels, manifested as a dysfunction of sympathetic and sensory-motor nerves. Furthermore, the graded destruction of nerve types, such that damage occurred in the order: CGRP-IR greater than NA greater than SP-IR, indicated a differential sensitivity of different nerves to this toxin.
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PMID:Acrylamide-induced autonomic neuropathy of rat mesenteric vessels: histological and pharmacological studies. 194 19

Five unique, high affinity rabbit polyclonal antibodies against neuromedin B were characterized in a radioimmunoassay in terms of the following parameters: pH and type of buffer, ionic strength, and non-ionic detergents in order to optimize immunoglobulin-peptide interaction; specificity using peptides of the bombesin family, in addition to the tachykinin substance P; and affinity to neuromedin B. Optimum conditions included acidic pH (5.25), high ionic strength (greater than 0.1 M) and absence of non-ionic detergents, which inhibited the assay. Affinities for the 5 antibodies ranged from 10 to 48 fmol neuromedin B with titers from 1:1,000 to 1:10,000 and the sequence-specificity covered the entire peptide; cross-reactivity towards substance P was negligible. As a model tissue, rat spinal cord was homogenized with 5 different extraction solvents, including acetone, methanol, acid and alkaline conditions, and assayed by each polyclonal antiserum; neuromedin B immunoreactivity levels were highest in acid and alkaline extracts and reflected the specificity of the antibody used. Applying these antisera to rat brain extracts, the posterior pituitary gland contained the highest concentration of immunoreactive equivalents of neuromedin B followed by the anterior pituitary, hypothalamus, and hippocampus. The immunoreactive content in the pituitary and hypothalamus, however, depended on the particular antisera used with significant (P less than 0.01) differences existing between them. Further application of these polyclonal antibodies to a spinal cord extract analyzed by isocratic reverse-phase HPLC conditions also revealed differences in their cross-reactivity with the immunoreactive peptides. These antisera may now be used as molecular probes for the determination of extractable immunoreactive neuromedin B from neural tissue and in situ localization by immunohistochemical techniques.
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PMID:Assessment of neuromedin B polyclonal antibodies as molecular probes in neural tissue. 335 56

The effect of acute and subchronic acrylamide treatment on levels of dopamine, serotonin, and their metabolites was determined in several brain regions of the rat. Concentrations of several neuropeptides and circulating hormones were also measured. Both a single and repeated doses of acrylamide resulted in elevated levels of 5-hydroxyindolacetic acid in all regions studied (frontal cortex, striatum, hippocampus, brain stem, and hypothalamus). Changes in regional content of other monoamines were much less pronounced. Turnover studies following pargyline blockage of monoamine oxidase, suggested results were due to increased rates of serotonin turnover in acrylamide-treated rats. Changes in neuropeptide levels were only detected in the hypothalamus where a single acrylamide treatment caused elevated levels of beta-endorphin and substance P, and in frontal cortex where met-enkephalin levels were higher after repeated acrylamide injection. Such repeated injection caused a major depression in plasma levels of testosterone and prolactin.
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PMID:Effect of acrylamide on neurotransmitter metabolism and neuropeptide levels in several brain regions and upon circulating hormones. 618 40

A highly purified preparation of a cation-sensitive neutral endopeptidase was obtained from bovine pituitaries. The enzyme constitutes almost 0.1% of the protein in bovine pituitary homogenates. Polyacrylamide gel electrophoresis of the enzyme showed a single protein band, and in gel filtration experiments on calibrated Sepharose 6B columns the enzyme eluted slightly ahead of thyroglobulin, suggesting an apparent molecular weight of about 700,000. Polyacrylamide gel electrophoresis in SDS-containing buffers indicated the presence of three major components with molecular weights ranging from about 24,000 to 28,000. The enzyme hydrolyzes bonds between hydrophobic and small neutral amino acids in both model synthetic substrates and biologically active peptides such as substance P, LH-RH, and bradykinin. Peptide bonds in which the carbonyl group is contributed by a glutamyl or arginyl residue are also hydrolyzed, especially if they are preceded in the sequence by hydrophobic amino acids. Leupeptin exclusively inhibited enzymatic activity toward the arginine-containing substrates. This observation, together with the high molecular weight and broad specificity of the enzyme, raised the possibility that the isolated enzyme represents a proteolytic complex composed of units with distinctly different activities. Preliminary attempts to dissociate the enzyme into catalytic units of lower molecular weight were not successful and led to loss of activity.
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PMID:Cation-sensitive neutral endopeptidase: isolation and specificity of the bovine pituitary enzyme. 677 72

The effects of chronic administration of acrylamide on sympathetic and sensory nerves were examined in the mesenteric artery of rabbits. The noradrenaline (NA) content of the artery was significantly decreased and the total contractile response to electrical field stimulation (4-64 Hz) markedly reduced in the acrylamide group. This was not due to an impairment of the contractility of the smooth muscle or to alterations in the postjunctional receptors. At 16 Hz, only the purinergic component of sympathetic cotransmission was significantly reduced by acrylamide. At 64 Hz, both the purinergic and the adrenergic components were significantly decreased. Field stimulation of the artery pretreated with guanethidine and precontracted with NA produced a frequency-dependent relaxation which was prevented by capsaicin and thus mediated by perivascular sensory nerves. In contrast to its effects on sympathetic cotransmission, acrylamide resulted in a trend, although not significant, towards increased responses at each frequency studied (2-16 Hz). 2-Methylthio-ATP (2Me-S-ATP) caused significantly greater relaxation following acrylamide treatment while vasodilator responses to calcitonin gene-related peptide and substance P were unchanged. It is concluded that, in addition to its known action in producing neuropathy in myelinated somatic motor and sensory nerves, acrylamide causes damage to unmyelinated perivascular sympathetic fibres. Purinergic mechanisms may be particularly susceptible to acrylamide since both the purinergic component of sympathetic vasoconstriction and the relaxation in response to 2Me-S-ATP were affected by acrylamide treatment.
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PMID:Effects of acrylamide on cotransmission in perivascular sympathetic and sensory nerves. 780 72

The effect of acrylamide intoxication (a widely used model for autonomic neuropathy) on the fluorescence intensity and density of catecholamine- and peptide-containing nerve fibres and tissue content of noradrenaline and the peptides vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P and neuropeptide Y in the enteric nerves of rat ileum was examined. Histochemical and immunohistochemical techniques were used to localize catecholamine- and peptide-containing nerve fibres. The tissue content of noradrenaline was measured using high-performance liquid chromatography, and an enzyme-linked immunosorbent assay technique was used to determine the tissue content of the peptides investigated. Acrylamide intoxication caused a significant decrease in the density of catecholamine-containing nerve fibres and tissue content of noradrenaline in the myenteric plexus of rat ileum. A decrease in tissue content and immunoreactivity of calcitonin gene-related peptide and an increase in vasoactive intestinal polypeptide was seen in the myenteric plexus of ileum from acrylamide-intoxicated rats. In the submucous plexus, the acrylamide treatment caused a decrease in calcitonin gene-related peptide immunoreactivity and an increase in vasoactive intestinal polypeptide and neuropeptide Y immunoreactivity. There was no change in either tissue content or immunoreactivity of substance P in both myenteric and submucous plexuses of the treated rat ileum. These changes have a striking similarity with those found in the enteric nerves of streptozotocin-diabetic rat ileum, suggesting the possible presence of an underlying common mechanism(s) in the development of neuropathic changes in the autonomic nerves of acrylamide-intoxicated and streptozotocin-diabetic rats.
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PMID:Acrylamide-induced neuropathic changes in rat enteric nerves: similarities with effects of streptozotocin-diabetes. 874 Jun 60

The distribution of tachykinin receptors in guinea-pig airways was studied using newly developed selective radioligands, [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]neurokinin A-(4-10) for NK2 receptors and [125I]Bolton-Hunter-[Sar9,Met(O2)11]substance P for NK1 receptors. Optimum incubation times were 60 and 45 min for tachykinin NK2 and NK1 sites, respectively, in slide-mounted sections of guinea-pig lung. Bacitracin (40 micrograms/ml) greatly reduced specific binding of [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]neurokinin A-(4-10), whereas phosphoramidon (1 and 10 microM) and bacitracin (40 micrograms/ml) significantly increased the specific binding of [125I]Bolton-Hunter-[Sar9,Met(O2)11]substance P. Dense specific binding of [125I]Bolton-Hunter-[Sar9,Met(O2)11]substance P occurred over bronchial smooth muscle of large and small airways, with moderate binding on bronchial epithelium and over pulmonary arterial smooth muscle. Moderate specific binding of [125I][Lys5,Tyr(I2)7, MeLeu9,Nle10]neurokinin A-(4-10) was associated with bronchial smooth muscle of mainly large airways but not with other histological regions. This is the first autoradiographic report of (a low density of) tachykinin NK2 binding sites on airway smooth muscle and supports the potent actions of NK2 receptor ligands as contractile agents in guinea-pig isolated bronchi.
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PMID:Autoradiographic localization of tachykinin NK2 and NK1 receptors in the guinea-pig lung, using selective radioligands. 889 98


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