Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We have investigated neurotransmitter-related markers of the cerebrospinal fluid (CSF) in a carefully screened series of normally aging subjects in standardized conditions in order to find out the influence of age and other confounding factors on CSF measures. The levels of 3-methoxy-4-hydroxyglycol (MHPG) and the activity of acetylcholinesterase (AChE) also increased with age, while homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5 HIAA) and immunoreactivities of somatostatin (SLI), beta-endorphin (BLI) and adrenocorticotropic hormone (ACTH) were unrelated to age. The gender of subjects had no significant effect on the levels of neurotransmitter markers, while seasonal changes, as well as height and weight of the subjects seemed to cause some variations in the levels of HVA, dopamine-beta-hydroxylase (DBH) and ACTH. The study underscores the importance of standardized conditions and matched patient groups in the CSF studies.
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PMID:Neurotransmitter markers in the cerebrospinal fluid of normal subjects. Effects of aging and other confounding factors. 167 57

Serum adrenocorticotropic hormone (ACTH) and growth hormone (GH) concentrations were assessed simultaneously with hypothalamic neuronal activities of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) 60 min after the third cerebroventricular administration of neostigmine (a cholinesterase inhibitor) in awake rats. Serum ACTH and GH concentrations were significantly increased and decreased, respectively. Neostigmine caused significant increases in hypothalamic NE and DA activities and a significant decrease in hypothalamic 5-HT activity. The reciprocal changes of serum ACTH and GH concentrations were similar to those of hypothalamic NE and 5-HT activities. Multiple regression analyses with stepwise procedure revealed that hypothalamic NE and 5-HT activities were respectively significant determinants of serum ACTH and GH concentrations. Apart from the direct influence of neostigmine on ACTH and GH secretions, it is suggested that the changes in hypothalamic monoaminergic activities play an important role in modulating ACTH and GH secretions following the administration of neostigmine.
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PMID:Adrenocorticotropin and growth hormone secretions after intracerebroventricular administration of neostigmine in rats: their relationships to hypothalamic monoaminergic neuronal activities. 782 Jun 71

Alterations of neuroendocrinological indices determined by the impaired regulating effects of cholinergic neurotransmission have been described in primary dementia. In this study we have evaluated the effects of acetylcholinesterase inhibition by pyridostigmine on growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7 patients with primary degenerative dementia and in 8 sex- and age-matched controls. Demented subjects showed higher cortisol basal levels and lower ACTH levels than controls. Pyridostigmine increased the GH response to GHRH in both groups, the effect being significantly enhanced in patients. An increase of ACTH and cortisol levels was found in both groups after pyridostigmine and CRH administration. Pyridostigmine pretreatment significantly increased the ACTH response to CRH in controls but not in patients. The obtained data may indicate that a muscarinic receptor upregulation and an impairment of somatostatinergic function are operative in the regulation of GH secretion in dementia. An underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the responses of ACTH and cortisol to CRH in this disorder.
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PMID:Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone-releasing hormone on the pituitary-adrenal axis and on growth hormone secretion in dementia. 827 99

We asked whether hypothalamic-pituitary-adrenocortical (HPA) axis responses to a cholinergic stimulus are blunted in patients with Alzheimer's disease (AD) of mild to moderate severity. Such a finding would be consistent with a central cholinergic deficiency early in the course of AD. To address this question, we measured the plasma adrenocorticotropic hormone (ACTH), beta-endorphin-like immunoreactivity (beta E-LI), and cortisol responses to the cholinesterase inhibitor physostigmine in 10 healthy normal older subjects (age = 71 +/- 2 years) and 11 outpatients with probable AD (age = 72 +/- 2 years; Mini Mental State Exam score = 19 +/- 2). Cortisol concentrations were higher in AD subjects throughout the study, but AD and normal older subjects had similar robust ACTH, beta E-LI, and cortisol responses to physostigmine. In all subjects combined, women had greater ACTH, beta E-LI, and cortisol responses to physostigmine than did men. Plasma physostigmine concentrations did not differ between groups. These results suggest that female gender enhances the magnitude of HPA axis responses to cholinergic stimulation in older humans; however, the HPA axis response to physostigmine does not appear to reflect central cholinergic deficiency in the early stages of AD.
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PMID:Hypothalamic-pituitary-adrenocortical axis responses to physostigmine: effects of Alzheimer's disease and gender. 878 Aug 56

The hypothalamic-pituitary-adrenal (HPA) axis has differential physiological activity in male and female animals (sexual diergism). Central cholinergic systems stimulate this endocrine axis. In the present study we investigated muscarinic and nicotinic cholinergic influences on HPA axis activity in male and female rats by pretreatment with selective cholinergic receptor antagonists followed by stimulation with physostigmine (PHYSO), an acetylcholinesterase inhibitor. Hormonal measures were plasma arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Male rats had significantly greater AVP and ACTH responses to PHYSO alone than did females. Scopolamine (SCOP) enhanced the AVP response to PHYSO to a greater extent in males than in females. In contrast, mecamylamine (MEC) enhanced the AVP response in females but decreased it in males. SCOP potentiated, and MEC inhibited, the stimulatory effect of PHYSO on ACTH in both sexes, but SCOP potentiation was greater in males, and MEC inhibition was greater in females. Absolute CORT increases following PHYSO were greater in females, but percent increases over baseline were greater in males. Similar to their effects on ACTH responses, MEC attenuated, and SCOP enhanced, CORT responses to PHYSO. These results suggest that cholinergic receptor subtypes may influence HPA axis activity differentially in male and female rats.
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PMID:Sexual diergism in rat hypothalamic-pituitary-adrenal axis responses to cholinergic stimulation and antagonism. 1122 19

Hypothalamic-pituitary-adrenal (HPA) axis responsiveness differs physiologically and pharmacologically between the sexes (sexual diergism). Central nicotinic receptors modulate this endocrine axis. Previous studies have established that nicotine (NIC) stimulates the HPA axis; however, only male animals have been used. We have demonstrated that plasma arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) concentrations showed greater responsiveness in male than in female rats pretreated with scopolamine (SCOP), a muscarinic antagonist, followed by physostigmine (PHYSO), an acetylcholinesterase inhibitor. These results suggest that the SCOP + PHYSO effects may have resulted from an indirect nicotinic effect caused by increased synaptic acetylcholine with simultaneous muscarinic antagonism. In the present study, we investigated nicotinic cholinergic influences on HPA axis activity in male and female rats by administering NIC (0, 0.03, 0.1, 0.3, or 0.5 mg/kg) and determining plasma AVP, ACTH, and corticosterone (CORT) responses. Male rats had a significantly greater, dose-related AVP response to NIC than did females. In contrast, female rats had significantly greater, dose-related ACTH and CORT responses to NIC than did males. Hormone responses following NIC were similar to hormone responses following SCOP + PHYSO. These results suggest nicotinic receptors influence the HPA axis differentially in male and female rats.
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PMID:Male-female differences in rat hypothalamic-pituitary-adrenal axis responses to nicotine stimulation. 1140 96

Central cholinergic systems differentially modulate hypothalamic-pituitary-adrenal (HPA) axis activity in female and male animals (sexual diergism). We previously reported that male rats had significantly greater HPA axis responses to stimulation by physostigmine (PHYSO), an acetylcholinesterase (AChE) inhibitor, compared to females. Females in defined estrous cycle stages, however, were not studied because of sample size limitations. We, therefore, determined HPA axis responses to stimulation by PHYSO in females during all estrous cycle stages (n = 78), and in male rats (n = 75). Plasma arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) were measured. Estrous cycle stage was determined by light microscopy of vaginal smears. Proestrous and estrous females had higher ACTH and CORT responses compared to metestrous and diestrous females. Males had higher ACTH and AVP responses compared to females in all cycle stages. CORT responses followed the ACTH responses, except that females started from a higher baseline in all estrous stages, compared to males. These results suggest that cholinergic regulation of the HPA axis differs among females across stages of the estrous cycle, as well as between males and females. These effects are likely due to differences in circulating sex steroids and their actions within the brain.
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PMID:Estrous cycle influences on sexual diergism of HPA axis responses to cholinergic stimulation in rats. 1243 52

Kai Xin San (KXS), a traditional Chinese herbal medicine, has been used clinically for the treatment of depressive disorders and cognitive impairment for centuries. However, the effects of KXS on cognitive dysfunction induced by depression have not been evaluated scientifically. The present study aimed to explore the antidepressant-like and nootropic effects of an aqueous extract of KXS (at doses of 0.3, 0.9, and 2.7 g/kg/day) using chronic mild stress (CMS) as a model of depression. Depressive symptoms were analyzed using the sucrose-preference and novelty-induced inhibition of feeding tests. Cognitive function was evaluated using a two-way active avoidance task. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels, acetylcholinesterase (AChE) protein expression in the hippocampus, and monoamine neurotransmitter concentrations in the prefrontal cortex and hippocampus were also determined to elucidate the neurochemical mechanisms. Experimental results showed that KXS aqueous extract significantly ameliorated the CMS-induced depressive symptoms, including the reduced preference index and prolonged latency to novelty-suppressed feeding. Simultaneously, KXS significantly reversed the CMS-induced decrease in the numbers of active avoidance and active movement distances and increase in the numbers of the passive avoidance and passive movement distances, thereby producing nootropic effects in the two-way active avoidance test. KXS also inhibited the increased AChE expression in the hippocampus, up-regulated the decreased monoamine neurotransmitter concentrations of both brain areas and reduced the elevated ACTH concentrations in the serum induced by CMS. Taken together, these results indicate that KXS exerts its antidepressant-like and nootropic effects in the CMS model by modulating the HPA axis, monoamine neurotransmitter and cholinergic systems.
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PMID:Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress. 1942 57

Acute gastrointestinal events (mostly manifested by nausea, vomiting, or loss of appetite) are class effects of all cholinesterase inhibitors, which are prescribed for the treatment of Alzheimer's disease. The underlying mechanism, however, has been unclear. Because corticotropin-releasing hormone is related to appetite control, we focused on the activation of the hypothalamo-pituitary-adrenal system and food intake following the administration of the cholinesterase inhibitor, donepezil, in rats. We monitored the plasma concentrations of adrenocorticotropic hormone, c-Fos, in the paraventricular nucleus, and intakes of rat chow for 3 h after the first administration of donepezil, and 2 weeks later, after daily administration of donepezil. The intragastric administration of 3 mg/kg of donepezil significantly increased the plasma adrenocorticotropic hormone levels and c-Fos expression in the paraventricular nucleus, and decreased the food intake on the first day. The increase in adrenocorticotropic hormone and loss of appetite after oral administration of the drug were attenuated after daily administration for 2 weeks.
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PMID:Responses of hypothalamo-pituitary-adrenal axis to a cholinesterase inhibitor. 1973 98

Central cholinergic systems regulate the hypothalamic-pituitary-adrenal (HPA) axis differentially in males and females (sexual diergism). We previously investigated the role of muscarinic receptors in this regulation by administering physostigmine (PHYSO), an acetylcholinesterase inhibitor, to male and female rats pretreated with scopolamine (SCOP), a nonselective muscarinic antagonist. SCOP pretreatment enhanced adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses in both sexes, but males had greater ACTH responses while females had greater CORT responses. In the present study, we further explored the role of muscarinic receptor subtypes in HPA axis regulation by administering PHYSO to male and female rats following SCOP or various doses of either the M1 or the M2 selective muscarinic receptor antagonists, pirenzepine (PIREN) or methoctramine (METHO). Blood was sampled before and at multiple times after PHYSO. ACTH and CORT were determined by highly specific immunoassays. M1 antagonism by PIREN prior to PHYSO resulted in sustained, dose-dependent increases in ACTH and CORT: ACTH responses were similar in both sexes, and CORT responses were greater in females. M2 antagonism by METHO prior to PHYSO resulted in overall decreases in ACTH and CORT: ACTH and CORT responses were higher in females but lower in both sexes than the hormone responses following PIREN or SCOP pretreatment. Area under the curve analyses supported these findings. These results suggest that specific muscarinic receptor subtypes differentially influence the HPA axis in a sexually diergic manner.
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PMID:Sexually diergic hypothalamic-pituitary-adrenal axis responses to selective and non-selective muscarinic antagonists prior to cholinergic stimulation by physostigmine in rats. 2912 91


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