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)

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

Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA-N-5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity and reduction of N-myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta) in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up-regulating RAR beta expression.
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PMID:Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells. 782 65

Pirenzepine, a muscarinic antagonist probably acting via stimulation of hypothalamic somatostatin release, abolishes the growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) rise in normal subjects but only blunts it in patients with anorexia nervosa (AN). This finding suggested the existence in AN of an alteration of cholinergic system and/or somatostatinergic tone. To further investigate these mechanisms, in 11 AN women patients (age 18.8 +/- 0.9 years; BMI 13.4 +/- 0.4) we studied the GH response alone (1 microgram/Kg IV as a bolus at 0 min) and combined with pyridostigmine (PD, 120 mg orally, 60 min before GHRH administration), a cholinesterase inhibitor, or arginine (ARG 30 g infused over 30 min starting at 0 min), two compounds probably acting via inhibition of hypothalamic somatostatin (SS) release. The GH response to GHRH preceded by a previous (120 min before) neurohormone administration also was studied. All these tests also were performed in 20 normal age-matched women (age 22.0 +/- 1.8 yrs; BMI20.1 +/- 2.4). Basal serum GH levels were higher in AN patients than in normal volunteers (NV) (10.3 +/- 3.4 versus 2.8 +/- 0.3 microgram/L; p < 0.001), whereas plasma IGF-I levels were lower in AN patients than in NV (43.3 +/- 10.6 versus 172.4 +/- 13.9 micrograms/L; p < 0.00001). In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [delta area under the curve (AUC) 1173.6 +/- 167.6 versus 834.6 +/- 188.1 micrograms/L/h]. The GH response to the second of two consecutive GHRH boluses was lower (p < 0.01) than that of the first one either in AN patients or in NV (67.6 +/- 27.4 and 53.1 +/- 25.7 micrograms/L/h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. 788 Sep 38

The aims of our study were to investigate the effect of the acetylcholinesterase inhibitor pyridostigmine (PD) administration on growth hormone (GH) secretion in acromegaly and to investigate the effects of PD on GH levels following an i.v. infusion of hydrocortisone in acromegaly. We studied five adult patients with active acromegaly, three men and two women with a mean age of 60 +/- 5 years (range 47-71 years) and a mean BMI of 27 +/- 0.7 kg/m2 (range 24-28 kg/m2). All the patients underwent: 1) placebo, 2 tablets po or 2) PD, 120 mg po, at time -60 plus a bolus i.v. injection of 100 mg hydrocortisone succinate in 2 ml saline at time 0 followed by an i.v. infusion of 250 mg hydrocortisone succinate in 250 ml saline from 0 to 120 min, or 3) PD, po or 4) placebo, po at time -60 plus a bolus i.v. injection of 2 ml saline followed by an i.v. infusion of 250 ml saline from 0 to 120 min. Serum GH values did not significantly change after PD administration compared to those during placebo treatment and with respect to baseline levels. In all of the acromegalic patients during hydrocortisone succinate infusion, GH values clearly decreased with respect to basal levels in varying degrees, with a nadir between 90 and 180 minutes after the beginning of hydrocortisone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of pyridostigmine on the hydrocortisone-mediated decrease of circulating growth hormone levels in acromegaly. 792 92

A suppressed growth hormone (GH) response to GH-releasing hormone (GHRH) in both lean and overweight type II diabetics has been reported. Pyridostigmine (PD), an acetylcholinesterase inhibitor, elicits GH secretion when administered alone and enhances the GH response to GHRH in normal subjects. The aim of our study was to evaluate the effect of PD on GHRH-stimulated GH secretion in both lean and obese type II diabetic patients. We studied 16 patients with type II diabetes mellitus (seven lean and nine obese). Eleven nondiabetic subjects (six lean and five obese) served as controls. Each subjects underwent treatment with (1) 120 mg PD orally or (2) 2 tablets of placebo orally, 60 minutes before intravenous (IV) injection of 100 micrograms GHRH-(1-29)NH2. We have found no significant differences in GH responses to GHRH between obese diabetics and obese controls. On the other hand, the absolute GH levels were significantly suppressed in lean type II diabetics compared with lean controls at 15 and 30 minutes after GHRH injection. Obese diabetic subjects had slightly but not significantly decreased GH responses to GHRH+PD compared with obese nondiabetic subjects (8.36 +/- 1.62 v 14.4 +/- 7.62 micrograms/L). Lean type II diabetics showed a blunted GH release after GHRH+PD compared with normal-weight healthy subjects (GH peaks, 15.77 +/- 2.17 v 40.88 +/- 6.17 micrograms/L, P < .05). PD enhanced significantly the GH response to GHRH in obese diabetics, obese controls, and non-obese controls (P < .05), but not in non-obese type II diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II Diabetic patients. 802 15

Cholinergic pathways in the central nervous system positively influence growth hormone (GH) secretion. In fact pyridostigmine, a cholinesterase inhibitor, enhances both basal and GH-releasing hormone (GHRH)-induced GH secretion while, conversely, pirenzepine, an antagonist of muscarinic M1 receptors, inhibits the GH response to GHRH and to other physiological and pharmacological stimuli. The effect of the cholinergic system on GH secretion probably takes place via inhibition of the release of endogenous somatostatin. In this study in 36 normal adults (26 males and 10 females, age 22-35 years) we compared the effects of three cholinesterase inhibitors (pyridostigmine, 120 mg p.o., n = 19; neostigmine, 10 micrograms/kg i.v., n = 6; physostigmine, 12.5 micrograms/kg i.v., n = 6) and bethanechol, a direct muscarinic receptor agonist that is mainly active on muscarinic M3 receptors (25 micrograms/kg i.v., n = 5), on both basal and GHRH (1 microgram/kg i.v.)-stimulated GH secretion. Pyridostigmine, neostigmine and physostigmine induced a significant GH increase (peak vs. basal levels, mean +/- S.E.: 10.4 +/- 1.6 vs. 0.6 +/- 0.2 micrograms/l, P = 0.0001; 13.3 +/- 1.2 vs. 0.5 +/- 1.1 micrograms/l, P = 0.004; and 14.9 +/- 3.1 vs. 2.7 +/- 1.1 micrograms/l, P = 0.025;, respectively). These drugs also induced a similar potentiation of the GH response to GHRH (peak: 48.3 +/- 5.6 vs. 16.2 +/- 2.2 micrograms/l, P = 0.0001; 49.2 +/- 2.2 vs. 19.9 +/- 5.1 micrograms/l, P = 0.006; and 76.9 +/- 12.4 vs. 18.1 +/- 5.3 micrograms/l, P = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of direct and indirect acetylcholine receptor agonists on growth hormone secretion in humans. 820 11

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

The aim of the present work was to evaluate the effect on the growth hormone (GH) secretion of eptastigmine, a new long-acting cholinesterase inhibitor, in unanesthetized beagle dogs. In a first study, 5 young dogs were given single doses (0.5, 1.0, and 2.0 mg/kg, i.m.) of the drug or saline in a randomized cross-over manner. Blood samples were collected immediately before and, at regular intervals, until 150 min after drug injection. GH plasma concentrations were determined by radioimmunoassay. Plasma cholinesterase activity was measured with a potentiometric method. There was a significant logistic relationship (r = 0.601, P < 0.01) between the administered dose of eptastigmine and the log-transformed areas under the GH plasma concentration-time curve (AUC) with a calculated ED50 for eptastigmine of 0.63 +/- 0.36 mg/kg. There was also a significant linear relationship (r = 0.630, P < 0.01) between log-transformed AUC of GH levels and AUC of plasma cholinesterase activity. In a second study we evaluate the ability of eptastigmine (2.0 mg/kg, i.m.) to potentiate the GH-releasing effect of the GH-releasing hormone (GHRH, 2.0 micrograms/kg, i.v.) in young and old dogs. Eptastigmine was administered 45 min before GHRH and blood collected every 15 min until 90 min after GHRH injection. In young dogs, maximum GH plasma levels (Cmax) were 6.1 +/- 1.0 ng/ml after GHRH compared to 22.5 +/- 2.3 ng/ml after GHRH preceded by eptastigmine (P < 0.01). In old animals, Cmax were 4.6 +/- 1.4 ng/ml after GHRH vs 13.2 +/- 7.4 ng/ml after combined administration of GHRH and eptastigmine (P < 0.05). These data indicate that eptastigmine is very effective in augmenting basal and stimulated GH secretion in old dog. The good activity also shown in old animals suggests a potential use of this drug to reverse the age-dependent decline in GH secretion responsible for many involutional changes of aging.
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PMID:Eptastigmine augments basal and GHRH-stimulated growth hormone release in young and old dogs. 833 17

The growth hormone response to the acetylcholinesterase inhibitor pyridostigmine was measured in nine normothymic outpatients who met DSM-III-R criteria for obsessive-compulsive disorder. The responses were significantly elevated when compared to those found in a healthy comparison group (N = 9). The data suggest that cholinergic supersensitivity is present in obsessive-compulsive disorder.
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PMID:Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity. 849 78

Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and activity of the autoimmune process involving a key enzyme (glutamic acid decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 micrograms GHRH(1-29)NH2. Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure, administration of 120 mg oral PD 60 minutes before IV injection of 100 micrograms GHRH. Diabetic subjects with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peaks after GHRH were significantly (rs = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.
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PMID:Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus. 910 40


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