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

With the Bodian method stained fibers were observed in the lobules of the rat liver and with the modified Karnovsky and Roots thiocholine method cholinesterase (presumably acetylcholinesterase (AChE))-positive nerve fibers were found in a pattern similar to that of the Bodian-stained fibers. The AChE-positive nerve fibers form a network in the liver lobules in close relation to hepatocytes and sinusoids. Fluorescent varicose nerve fibers demonstrated by the glyoxylic acid and Falck-Hillarp fluorescence methods were found only in the interlobular spaces associated with vessels. As no overlapping of distribution patterns of AChE-positive nerve fibers and fluorescent nerve fibers occurs, the AChE activity of the nerves of the liver lobules probably reflects the associated presence of acetylcholine in the nerve fibers. In consequence we suggest that nerves of the liver lobules belong to the autonomic parasympathetic nervous system. SEM of liver tissue revealed light cords apparently situated in smooth-surfaced channels between adjacent hepatocytes and in the space of Disse, where fibers also cross sinusoids. We tentatively suggest that the cords of the SEM represent the AChE-positive nerve fibers of our LM observations.
 ...
PMID:On the intrinsic innervation of normal rat liver. Histochemical and scanning electron microscopical studies. 97 10

The neuromodulatory action of chlorothiazide (CTZ) was investigated in isolated rabbit bronchial smooth muscle (BSM) segments contracted with electrical field stimulation (ES). The tissues were placed in organ baths and stimulated with ES frequencies ranging from 1 to 75 Hz. CTZ (10(-4) to 10(-3) M) produced dose-dependent increases in ES-induced contractions. In the presence of 10(-3) M CTZ, the mean +/- SEM maximal tension (Tmax) induced by ES increased significantly (p less than 0.03) from 292.8 +/- 39.5 to 363.0 +/- 58.5 g/g tissue. BSM sensitivity to ES, expressed as the log ES frequency producing 50% of Tmax (i.e., log ES50) was also increased (p less than 0.001) in the presence of CTZ as indicated by a fall in the mean +/- SEM log ES50 from 1.05 +/- 0.05 to 0.804 +/- 0.09 Hz. The potentiating effect of CTZ on ES-induced contractions was independently blocked by either the neurotoxin, tetrodotoxin (4 x 10(-6) M), or the cholinergic antagonist, atropine (10(-5) M). In the presence of CTZ, the mean Tmax response to acetylcholine (ACh) was unaffected, whereas BSM sensitivity to the agonist increased significantly (p less than 0.001). On the other hand, the dose-response relationship to carbachol, a cholinergic agonist resistant to cholinesterase degradation, was unaffected by CTZ. In tissues pretreated with 10(-5) M neostigmine, an acetylcholinesterase (AChase) inhibitor, CTZ did not further augment either ES- or ACh-induced contractions. Taken together, these findings suggested that CTZ might be acting as an AChase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effect of chlorothiazide on neurally mediated contraction of rabbit bronchial smooth muscle. 173 3

Subjects with Cushing's disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushing's disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushing's disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushing's disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushing's disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushing's disease.
 ...
PMID:Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease. 180 75

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.
 ...
PMID:Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children. 199 16

OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.
 ...
PMID:Pyridostigmine fails to increase either spontaneous or GHRH-stimulated GH secretion during day or night in growth hormone-insufficient children. 206 Jan 50

The aim of this study was to verify that the stimulatory effect of cholinergic agonists on both basal and stimulated GH release observed in the morning persists in the night. The effects of pyridostigmine (120 mg orally), a cholinesterase inhibitor, on both basal and GHRH (1 micrograms/kg iv)-induced GH secretion were studied in 8 healthy volunteers, aged 22-30 years. In the morning, administration of pyridostigmine induced a significant increase in basal GH levels compared with saline (area under the response curve, mean +/- SEM: 277.0 +/- 54.0 vs 49.7 +/- 8.2 micrograms.l-1.h-1, p less than 0.02) as well as a strong potentiation of the GHRH-induced GH release (2117.6 +/- 353.0 vs 427.9 +/- 87.0 micrograms.l-h-1, p less than 0.02). In the night, GH secretion after pyridostigmine did not differ from saline (194.5 +/- 21.9 vs 89.4 +/- 28.7 micrograms.l-1.h-1). Moreover pyridostigmine failed to potentiate the GHRH-induced GH increase (1071.9 +/- 170.4 vs 740.2 +/- 150.9 micrograms.l-1.h-1). The pyridostigmine + GHRH-induced GH rise during the night was lower (p less than 0.05) than in the morning. All together, these data seem to indicate that cholinergic neurons controlling GH secretion are already maximally stimulated at night. As cholinergic activity negatively modulates SRIH secretion, our findings suggest that a reduced somatostatinergic tone in the hypothalamus is present during the night.
 ...
PMID:Failure of pyridostigmine to increase both basal and GHRH-induced GH secretion in the night. 210 88

Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 micrograms iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 +/- 4 vs 44 +/- 16 micrograms/l; mean +/- SEM). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 +/- 5 vs 77 +/- 20 micrograms/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.
 ...
PMID:Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects. 210 45

The effect of therapeutic range ultrasound (1 MHz) on skin permeation of D-mannitol, a highly polar sugar alcohol, inulin, a high molecular weight polysaccharide and physostigmine, a lipophilic anticholinesterase drug was studied in rats and guinea pigs. D-Mannitol and inulin are totally and rapidly excreted, once they have penetrated through the skin into the blood stream, permitting direct in vivo monitoring. For evaluating skin penetration of physostigmine the decrease of whole blood cholinesterase was measured. Ultrasound nearly completely eliminated the lag time usually associated with transdermal delivery of drugs. 3-5 min of ultrasound irradiation (1.5 W/cm2 continuous wave or 3 W/cm2 pulsed wave) increased the transdermal permeation of inulin and mannitol in rats by 5-20-fold within 1-2 h following ultrasound application. Ultrasound treatment also significantly increased (P less than 0.05) the inhibition of cholinesterase during the first hour after application in both physostigmine treated rats and guinea pigs: while in control guinea pigs no significant inhibition of cholinesterase could be detected during the first 2 h after application of physostigmine, the ultrasound treated group showed a 15 +/- 5% (mean +/- SEM) decrease in blood cholinesterase 1 h after ultrasound application. For physostigmine-treated rats the level of cholinesterase inhibition 1 h after ultrasound application was 53 +/- 5% in the ultrasound-treated group and 35 +/- 5% in the controls.
 ...
PMID:Effect of ultrasound on transdermal drug delivery to rats and guinea pigs. 249 96

In normal adults, repeated GHRH administration leads to progressively decreasing somatotrope responses. To verify whether this GH secretory pattern also connotes normal growing children, we have studied the effects of two consecutive (every 120 min) 1 microgram/kg iv GHRH boluses on GH release in normal adults (N = 7, age 23.2-30.6 years) children (N = 6, age 10.4-13.2 years). In the adults, the GH response to the second GHRH bolus (peak, mean +/- SEM; 2.9 +/- 0.8 micrograms/l) was lower (P less than 0.02) than that to the first bolus (15.9 +/- 2.4 micrograms/l). Conversely, in children the GH response to the second GHRH bolus (25.6 +/- 6.3 micrograms/l) overrode the first one (13.6 +/- 6.5 micrograms/l), but this difference did not attain statistical significance. In adults cholinergic enhancement by pyridostigmine, a cholinesterase inhibitor, was previously shown to re-instate, even to potentiate somatotrope responsiveness to consecutive GHRH boluses. Thus, in 5 children GH response to repeated GHRH boluses was retested administering pyridostigmine (60 mg orally) 30 min before the second GHRH bolus. In these subjects, pyridostigmine failed significantly to potentiate the GH responsiveness to the second GHRH bolus (30.3 +/- 4.6 vs 25.0 +/- 7.6 micrograms/l). These data indicate that differently from in adults, in children repeated GHRH administration does not reduce somatotrope responsiveness and that cholinergic enhancement fails to potentiate GH responsiveness to the second GHRH bolus.
 ...
PMID:Repeated GH-releasing hormone administration unravels different GH secretory patterns in normal adults and children. 249 48

In obesity the reduced growth hormone (GH) responses to several provocative stimuli including growth hormone-releasing hormone (GHRH) indicate a diminished somatotroph responsiveness but do not distinguish between primary pituitary and hypothalamic pathogenesis. However, it has been shown that the cholinergic system positively influences Gh secretion likely by modulating somatostatin release in a negative way. Thus, the effect of cholinergic activity enhancement by pyridostigmine (PD), an acetylcholinesterase inhibitor, on both basal and GHRH-induced GH secretion was studied in 14 obese subjects (eight adults and six children). Eighteen nonobese subjects (seven adults and 11 children) were studied as controls. In obese subjects the GHRH-induced GH increase was lower than in controls (peak, mean +/- SEM, adults, 9.2 +/- 2.7 v 16.8 +/- 5.7 ng/mL; children, 8.0 +/- 0.8 v 20.3 +/- 4.6 ng/mL) attaining statistical significance only in children group (P less than .02). The PD-induced GH response in the two obese groups was similar to that observed in relative controls (adults, 5.3 +/- 1.0 v 7.4 +/- 1.7 ng/mL; children, 9.6 +/- 1.6 v 13.3 +/- 1.4 ng/mL). PD clearly potentiated the GH response to GHRH in obese subjects, both adults (P less than .05 v GHRH alone) and children (P less than .0005 v GHRH alone). However, the GH responses to PD + GHRH was significantly reduced in obese subjects compared with controls (adults, 18.1 +/- 2.2 v 42.7 +/- 10.7 ng/mL, P less than .05; children, 28.3 +/- 4.5 v 58.2 +/- 7.7 ng/mL, P less than .01). In conclusion, PD is able to potentiate the blunted GH responses to GHRH in obese adults and children, inducing a GH increase similar to that observed after GHRH alone in normal subjects. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in obesity.
 ...
PMID:Effect of cholinergic enhancement by pyridostigmine on growth hormone secretion in obese adults and children. 250 May 77


1 2 3 4 5 6 7 Next >>