Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.
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PMID:Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats. 287 43

CSF neurotransmitter markers may reflect neurochemical alterations in Alzheimer's disease (AD). The best studied neurochemical deficit in AD is that of acetylcholine. Both acetylcholinesterase and butyrylcholinesterase activity have been reported to be reduced in some but not all studies of AD CSF. Studies of monoamine metabolites have also been controversial but most authors have found reduced concentrations of CSF HVA, lesser reductions in HIAA and no change in MHPG. CSF GABA concentrations have been found to be reduced in AD. Studies of CSF neuropeptides in AD have shown reduced concentrations of somatostatin and vasopressin, normal concentrations of vasoactive intestinal polypeptide and either normal or decreased concentrations of beta-endorphin and corticotropin releasing factor. Although no individual CSF neurochemical markers are specific for AD it may be possible to develop a profile of several neurochemical markers which will have enhanced specificity.
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PMID:CSF neurotransmitter markers in Alzheimer's disease. 287 17

This study examined the amygdaloid complex in Alzheimer's disease (AD). We compared the distribution and morphology of somatostatin (SOM-) and neuropeptide Y-immunoreactive (NPY-IR) neurons in the amygdala with the distribution of neuritic plaques (NP) and acetylcholinesterase (AChE) staining patterns in various subnuclei. We found that in AD, there was an increase in the number of small, atrophic neurons for both SOM and NPY, and subregional analysis revealed similar size reductions in all subnuclei. In contrast, the highest density of NP was found in the corticomedial nuclei and densest staining for AChE in the basal nucleus. Although NPY- and SOM-IR fibers were occasionally associated with NP, a dense, morphologically preserved peptidergic fiber-network was found in all areas including subnuclei with high numbers of NP. Our study indicates that atrophic SOM- and NPY-IR neurons are not correlated with the subregional distribution of NP or cholinesterase staining pattern of the amygdala, and suggests that alterations in SOM and NPY neurons are not characteristics of the primary pathogenic process that underlie the formation of NP or cholinergic cell loss in AD.
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PMID:Neuropeptides and neuropathology in the amygdala in Alzheimer's disease: relationship between somatostatin, neuropeptide Y and subregional distribution of neuritic plaques. 290 51

In a double-blind, placebo-controlled study, the central nervous system effects of an ACTH4-9 analog, Org2766 (40 mg/day), in Alzheimer's disease were assessed by measuring cerebrospinal fluid parameters during 6 months' treatment. Somatostatin-like immunoreactivity and cholinesterase activity, which are known to be reduced in cerebrospinal fluid of Alzheimer patients compared with controls, did not change during treatment. As a marker of noradrenergic and dopaminergic systems, we measured dopamine-beta-hydroxylase and homovanillic acid, but both levels were static. These results suggest that Org2766 did not interact with the transmitter systems, which are thought to be disturbed in Alzheimer's disease.
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PMID:The effect of ACTH4-9 analog (Org2766) on some cerebrospinal fluid parameters in patients with Alzheimer's disease. 299 89

Cholinesterase (ChE) activity and somatostatin-like immunoreactivity (SLI) of the cerebrospinal fluid were determined for 59 patients with dementia of the Alzheimer type (AD/SDAT) and for 19 age-matched control patients with no signs of dementia. Both ChE activities and SLI concentrations of cerebrospinal fluid were reduced significantly in dementia patients compared to the controls. In the AD/SDAT patients cholinesterase and somatostatin-like immunoreactivity levels seemed to be correlated with the severity of dementia. These findings agree with observations of reduced cortical acetylcholinesterase activities and somatostatin values in dementia of the Alzheimer type.
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PMID:Reduced cholinesterase activity and somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with dementia of the Alzheimer type. 614 29

Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 micrograms of TRH i.v.; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 micrograms of octreotide (SMS) i.v.; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST-TRH test.
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PMID:Combined pyridostigmine-thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men. 758 70

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

To indirectly evaluate the hypothalamic somatostatin (SS) tone in patients with acromegaly, the effects of pyridostigmine (PD), a cholinesterase inhibitor which can inhibit hypothalamic SS secretion, on TRH-induced TSH secretion and the effects of SMS 201-995 on TSH or GH secretion were studied in acromegalic patients (31-69 yr, n = 10), normal young (21-24 yr, n = 7) and normal old male subjects (62-71 yr, n = 7). After pretreatment with PD (60 mg po, -30 min), normal young subjects showed significantly enhanced TSH responses to TRH (500 micrograms i.v., 0 min) compared to single administration of TRH, whereas normal old and acromegalic patients did not show such enhancement. Plasma TSH response to a single administration of TRH in acromegalic patients was significantly lower than that of normal young and old subjects. Although normal young and old subjects showed significantly enhanced GH responses to GHRH (100 micrograms i.v. at 0 min) after the pretreatment with PD (60 mg, -30 min), no such enhancement was observed in acromegalic patients. In contrast, the decrement in plasma TSH after SMS 201-995 administration was similar between normal subjects (5 young 5 old) and 7 acromegalic patients. Further, the maximal plasma GH decrement after administration was significantly greater in acromegalic patients than in the 5 normal young and 5 old subjects p < 0.01). In conclusion, hypothalamic SS tone does not appear to be elevated in acromegalic patients compared to normal young and probably old subjects.
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PMID:The evaluation of hypothalamic somatostatin tone using pyridostigmine and thyrotropin releasing hormone in patients with acromegaly. 791 36

Heart rate is regulated by the autonomic nervous system but little is known about the pattern of innervation of the pacemaker in the sinoatrial node, or the subpopulations of nerves involved. Therefore in this study the pacemaker was located using electrophysiological methods and the pattern of innervation established by cholinesterase staining. In subsequent experiments, subpopulations of sympathetic, sensory and parasympathetic nerves were identified. Sympathetic nerves were labelled by glyoxylic acid-induced catecholamine fluorescence or an antiserum raised against tyrosine hydroxylase (TH). These experiments showed that the entire sinoatrial node was densely innervated by sympathetic axons, the majority of which were immunoreactive for neuropeptide Y (NPY). There were a few axons which were only immunoreactive for TH. Sensory nerves which were immunoreactive for both substance P (SP) and calcitonin gene-related peptide (CGRP) were also found throughout the sinoatrial node. In the absence of a selective marker for parasympathetic neurons, hearts were extrinsically denervated by placing them in organotypic culture to allow degeneration of extrinsic axons. In this way intrinsic parasympathetic neurons could be characterised. These experiments revealed several distinct populations of parasympathetic nerves which innervated only a small, discrete part of the sinoatrial node. These populations were immunoreactive for NPY, somatostatin (SOM) or vasoactive intestinal peptide (VIP) alone, or SOM combined with NPY, SOM with dynorphin B, and SOM with SP. These results highlight a remarkable difference in the pattern of innervation of the sinoatrial node by the sympathetic and parasympathetic nervous systems. Furthermore the presence of several distinct populations of autonomic cardiac neurons indicates a further complexity in neuronal regulation of heart rate.
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PMID:Innervation of the pacemaker in guinea-pig sinoatrial node. 801 78

GH secretion is stimulated by the administration of cholinesterase inhibitors (such as pyridostigmine and neostigmine) in several species, including man. On the basis of indirect experiments, it has been postulated that this action is mediated by a decrease in hypothalamic somatostatin release. We have investigated the effect of neostigmine in sheep, since it is possible to collect hypophysial portal blood for GH-releasing hormone (GHRH) and somatostatin determination in this species under a conscious unstressed state. First, after i.v. injection of neostigmine (1 mg), a significant increase in plasma GH levels and an unequivocal potentiation of the GH response to GHRH were observed. Then, we observed that i.v. injection of neostigmine (1 mg) induced an immediate, short-lasting (30 min), and marked increase in GHRH (126.1 +/- 17 vs. 14.5 +/- 2.1 pg/ml; P < 0.01) levels in hypophysial portal blood of rams chronically implanted with perihypophysial cannulae. No change in somatostatin secretion was recorded during the same period. These data suggest that the stimulating effect of cholinergic drugs on GH secretion is mediated by stimulation of GHRH release. A direct effect of neostigmine at the level of pituitary gland is possible and may explain the potentiation of GHRH-induced GH release.
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PMID:Neostigmine stimulates growth hormone-releasing hormone release into hypophysial portal blood of conscious sheep. 809 14


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