Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH) secretion is blunted in diabetic rats. In the present experiment we observed that pituitary GH concentrations and the plasma GH response to an exogenous dose of growth hormone-releasing hormone (GHRH) is decreased in streptozotocin-induced diabetic rats (p less than 0.02) with respect to normal rats. In an attempt to determine if increased somatostatin (SRIF) secretion is responsible for the decreased GH secretion, we studied the effect of modulating SRIF tone on the GH response to GHRH in normal and streptozotocin-induced diabetic rats. Rats were pretreated with either normal sheep serum and saline (NSS+SAL), somatostatin antibodies (SRIF-Ab), or pyridostigmine (PD), an acetylcholinesterase inhibitor hypothesized to reduce hypothalamic SRIF secretion. Pretreatment of normal rats with SRIF-Ab or PD resulted in an increased GH response to exogenous GHRH in comparison to NSS+SAL-pretreated normal rats at 5 min postinjection. In contrast, pretreatment of diabetic rats with SRIF-Ab or PD did not alter the GH response to exogenous GHRH when compared to NSS+SAL-pretreated diabetic animals. These results suggest that the blunted GH response to exogenous GHRH observed in streptozotocin-induced diabetic rats may not be due to an increase of endogenous SRIF tone.
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PMID:Hypothalamic regulation of impaired growth hormone secretion in diabetic rats. 1. Studies in streptozotocin-induced diabetic rats. 135 66

We used the ELISA to measure the concentration of amyloid protein precursor with Kunitz type trypsin inhibitor domains (APPI) in CSF of dementia of the Alzheimer type (DAT) and examined the correlation of APPI with acetylcholinesterase (AChE) and somatostatin (SRIF). We found the APPI concentration in CSF of DAT to be significantly elevated compared with that of multi-infarct dementia and controls. We could significantly correlate APPI with AChE, but not correlate APPI with SRIF. The present results suggest that measurement of CSF APPI levels may be useful for diagnosis of DAT and the change of APPI may closely be associated with abnormality of acetylcholine system in DAT that has been reported.
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PMID:Amyloid beta protein precursors with kunitz-type inhibitor domains and acetylcholinesterase in cerebrospinal fluid from patients with dementia of the Alzheimer type. 137 55

Through an epidemiological survey, we observed 3 types of clinical courses among patients with senile dementia of the Alzheimer type (SDAT). The mental ability of the patients declined rapidly (Group A; n = 11), gradually (Group B; n = 6), or showed extremely slow changes (Group C; n = 9). The acetylcholinesterase (AChE) activity and somatostatin (SRIF) concentration of the cerebrospinal fluid (CSF) were measured in patients with Alzheimer's disease (AD) and 3 types of SDAT. Both AChE activity and SRIF concentration of CSF were significantly lower in Group A and among patients with AD compared with age-matched control subjects. Both AChE activity and SRIF concentration of CSF were not significantly different in Groups B and C. This biochemical study confirmed our epidemiological finding that only the patients in Group A with SDAT closely resembled the clinical course of AD and may belong to the category of neurodegenerative disorders.
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PMID:Characterization of the course of senile dementia of the Alzheimer type using cerebrospinal fluid levels of acetylcholinesterase and somatostatin. 257 39

Capsaicin was applied locally to the sciatic or saphenous nerve, and the effects on axoplasmic transport, neurogenic plasma extravasation, and thermal pain were studied. Capsaicin (10 mg/ml) led to a complete block of axoplasmic transport of immunoreactive substance P (I-SP) and somatostatin (I-SRIF) in rat sciatic nerve without affecting the transport of noradrenaline or acetylcholinesterase. Inhibition of I-SP transport was also found in sciatic nerves of guinea-pig, cat and rabbit. In contrast, one or two weeks after systemic capsaicin treatment (125 mg/kg s.c.), orthograde transport of I-SP was the same in control and capsaicin-treated rats. After local capsaicin application to the sciatic nerve, a decrease of I-SP was found not only in skin and sciatic nerve distal to the site of application, but also in dorsal root ganglia, dorsal roots and the dorsal half of the spinal cord segments L 4-5. This was accompanied by a loss of acid phosphatase activity in the substantia gelatinosa supplied by sciatic nerve afferents. Plasma extravasation by mustard oil was reduced in the skin of the hind paw with a time course identical to the I-SP depletion. The response to noxious heat (hot plate test) was, however, abolished earlier. These results indicate that capsaicin applied to a peripheral nerve inhibits axoplasmic transport in sensory but not in adrenergic or cholinergic neurons, which leads to long-term biochemical and functional changes of the entire sensory neuron. In addition, capsaicin appears to inhibit impulse propagation in certain populations of sensory neurons.
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PMID:Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin. 617 69

Cognitive and histological alterations in human Alzheimer's disease (AD) are correlated with selective neuronal loss in nucleus basalis of Meynert. In search of an animal model of AD-linked neurochemical deficits, we examined the effects of short- (2 weeks) and long- (3 and 6 months) term lesions of the nucleus basalis magnocellularis (NBM) on somatostatinergic parameters in rat forebrain. NBM lesions were performed by unilateral injection of ibotenic acid into the NBM. Cortical choline-acetyl transferase (ChAT) activity and acetylcholinesterase staining in the NBM remained significantly decreased ipsi- as compared to contralaterally up to 6 months after the placement of the lesion. Somatostatin (SRIF) content was increased by 120% in the ipsilateral frontal cortex 6 months post-lesion but not at shorter time intervals. Levels of neuropeptide Y (which is extensively co-localized with SRIF in the forebrain) were not significantly altered after unilateral NBM lesions at any time point. A 30% decrease in SRIF binding capacity as well as a marked reduction of SRIF inhibition of adenylate cyclase, indicative of a loss of functional SRIF receptors, was observed in ipsilateral versus contralateral frontal cortex on brain tissue homogenates after short-term unilateral NBM lesion. By film radioautography, the loss in SRIF binding sites was localized to both superficial and deep layers of the frontal cortex. This loss persisted up to 3 months but was no longer apparent after 6 months due to a decrease in SRIF binding capacity on the contralateral side.
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PMID:Short- and long-term effects of nucleus basalis magnocellularis lesions on cortical levels of somatostatin and its receptors in the rat. 809 61

The specific binding of 125I-Tyr11-somatostatin-14 (125I-Tyr11-SS-14) was measured in different cortical regions after unilateral ibotenic acid lesion of the rat nucleus basalis magnocellularis (NBM). A marked loss of acetylcholinesterase-positive fibers was observed in the frontal, parietal, temporal and occipital cortices ipsilateral to the lesion. The loss of cholinergic cell bodies in the NBM was further investigated with choline-acetyltransferase (ChAT) immunohistochemistry which indeed demonstrated a loss of ChAT-positive magnocellular perikarya. Autoradiographic analyses of specific binding of 125I-Tyr11-SS-14 demonstrated a significant reduction in binding density in the denervated parts of the neocortex. The decrease in specific binding was most pronounced (40-50%) in the superficial layers (I-III) of the frontal, parietal and temporal cortices 2 and 4 weeks after lesion. A significant loss in 125I-Tyr11-SS-14 binding in the deeper layers was only observed in the frontal cortex after 2 and 4 weeks. In the occipital cortex a significant decrease was measured in the superficial layers only after 4 weeks. The specific binding in all cortical regions returned to normal after 6 weeks. The results suggested that 125I-Tyr11-SS-14 binding sites are localized on cholinergic afferents in the rat neocortex and that an up-regulation of number of binding sites, alternatively an increased binding affinity occurred with time after lesion.
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PMID:Decrease of somatostatin receptor binding in the rat cerebral cortex after ibotenic acid lesion of the nucleus basalis magnocellularis: a quantitative autoradiographic study. 831 62

The objectives of this investigation were to characterize neuropeptide-degrading enzymes on the surface of gastric muscle cells and to determine their physiological function. Neutral endopeptidase (NEP, EC 3.4.24.11) activity was measured using the fluorogenic substrate glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine. The NEP inhibitors phosphoramidon and DL-thiorphan (1 microM) inhibited degradation of the substrate by gastric muscle membranes by 100% and by freshly dispersed gastric muscle cells by 55-60%. The phosphoramidon or DL-thiorphan-inhibitable activity, attributed to NEP, of membranes was 112 +/- 4.0 pmol h-1 (micrograms protein)-1 and of cells was 4.2 +/- 0.8 nmol h-1 (10(6) cells)-1. This activity was associated with membranes prepared from cells and was not detected in the cytoplasm or in the cell incubation solution. Gastric muscle membranes were fractionated by electrophoresis and analysed by Western blotting using two NEP antisera. Both antisera recognized a protein in membranes with an electrophoretic mobility identical to that of recombinant human NEP and an apparent molecular mass of approximately 95 kDa. Neuropeptides were degraded by membranes with specific activities in the order of [Leu5]enkephalin > [Met5]enkephalin > gastrin-releasing peptide-10 (GRP-10) > [D-Ala2][Leu5]enkephalin > somatostatin-14. Phosphoramidon and DL-thiorphan similarly inhibited the degradation of GRP-10 (mean of 35% inhibition), somatostatin-14 (57%) and the aminopeptidase-resistant analogue, [D-Ala2][Leu5]enkephalin (75%). When aminopeptidases were inhibited with amastatin (10 microM) phosphoramidon inhibited degradation of [Leu5]enkephalin (54%) and [Met5]enkephalin (100%). Phosphoramidon increased the potency of the contractile effects of neuropeptides on muscle cells by > 280-fold for somatostatin-14, 17-fold for GRP-10, 18-fold for [Met5]enkephalin and 14-fold for [Leu5]enkephalin. The results show that an NEP-like enzyme on the surface of gastric muscle cells degrades and inactivates enkephalins, GRP-10 and somatostatin-14 and acts in a manner analogous to that of acetylcholinesterase in the neuromuscular junction of skeletal muscle.
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PMID:Neutral endopeptidase (EC 3.4.24.11) modulates the contractile effects of neuropeptides on muscle cells from the guinea-pig stomach. 844 12