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

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
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PMID:Senile dementia of the Alzheimer type. 613 75

To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)1 and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed. This inhibition was blocked by D2 receptor blockade with metoclopramide or sulpiride, but not by D1 receptor blockade. Similarly, dopamine suppressed GH and PRL release by nonadenomatous pituitary cells in a dose-dependent manner, which was again blocked by D2 receptor blockade. The minimum effective concentration of dopamine required for a significant inhibition of PRL secretion (0.01 microM) was lower than that for GH release (0.1 microM). Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells. This effect was blocked by sulpiride, phentolamine, however, was ineffective. When TRH was added to the media, both GH and PRL secretion were enhanced in adenoma cells, while only the stimulation of PRL release was observed in nonadenomatous pituitary cells. Coincubation of TRH and dopamine resulted in variable effects on GH and PRL secretion. Somatostatin consistently lowered GH and PRL secretion in both adenomatous and nonadenomatous pituitary cells and completely blocked the TRH-induced stimulation of GH and PRL secretion from adenoma cells. Opioid peptides (1 microM) failed to affect hormone release. These results suggest that no qualitative difference in GH and PRL responses to dopaminergic agonists or to somatostatin exists between adenoma cells of acromegalic patients and normal pituitary cells, and that the direct effect of catecholamines on GH and PRL secretion from human pituitary cells is mediated mainly through dopamine receptor activation.
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PMID:Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture. 614 Feb 73

Norepinephrine is generally regarded as an inhibitor of insulin release. It has been shown, however, that under hyperglycemic circumstances, norepinephrine infused at a high dose may also stimulate insulin secretion. The goals of this study were, under normoglycemic conditions, to confirm this stimulatory effect and to determine whether a beta-adrenergic mechanism or central neural pathways were involved. Secretion of pancreatic somatostatin and glucagon were also studied. Fasted, anesthetized dogs had norepinephrine (2 micrograms X kg-1 X min-1) infused into a peripheral vein for 60 min; blood was sampled from the pancreaticoduodenal vein. Norepinephrine stimulated insulin, somatostatin, and glucagon secretion without significant changes in either blood glucose concentration or pancreaticoduodenal venous blood flow. The stimulatory effect of norepinephrine on the three hormones was abolished by propranolol pretreatment, thus implicating a beta-adrenergic mechanism. Because bilateral cervical vagotomy prevented stimulation of insulin secretion by norepinephrine, central neural pathways must have been involved in the stimulatory process. However, norepinephrine-induced glucagon secretion was not decreased by vagotomy, showing that the stimulation was due to either a direct action on the pancreatic A cell or of a central pathway not mediated via the vagus nerve. Norepinephrine-induced somatostatin secretion was partly reduced by vagotomy, indicating that several mechanisms could be implicated.
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PMID:In vivo stimulation of pancreatic hormone secretion by norepinephrine infusion in the dog. 614 71

Electrical field stimulation of the isolated pig bladder neck preparation initiated rapid non-adrenergic, non-cholinergic nerve-mediated relaxations. A wide range of substances were examined as possible candidates for the neurotransmitter involved. Of these, only 5-hydroxytryptamine, vasoactive intestinal polypeptide, adenosine and adenosine 5'-triphosphate produced relaxations. Noradrenaline, acetylcholine, substance P, bradykinin and angiotensin II caused contraction, while neurotensin, somatostatin, bombesin and gamma-amino butyric acid were without effect. The nerve response was not blocked by methysergide, ketanserin, chymotrypsin, apamin or 8-phenyltheophylline, although methysergide antagonised the responses to 5-hydroxytryptamine, chymotrypsin blocked the responses to VIP, and 8-phenyltheophylline antagonised the responses to adenosine and ATP.
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PMID:A novel non-adrenergic, non-cholinergic nerve-mediated relaxation of the pig bladder neck: an examination of possible neurotransmitter candidates. 614 1

Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.
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PMID:Mechanisms of catecholamine effects on ketogenesis. 614 93

Elevation of plasma norepinephrine concentrations to stress levels (1,800 pg/ml) resulted in normal subjects in a significant increase in ketone body production by 155% (determined by use of [14C]acetoacetate infusions), in a decrease of the metabolic clearance rate by 38%, hyperketonemia, and in increased plasma free fatty acid (FFA) levels by 57% after 75 min. Norepinephrine infusion during somatostatin-induced insulin deficiency resulted in an augmented and sustained increase in ketone body concentrations due to increased production and decreased peripheral clearance of ketone bodies. Norepinephrine's stimulatory effect on lipolysis waned with time, and its effect on ketogenesis in normal subjects was greater than its influence on plasma FFA levels, and thus presumably on hepatic FFA uptake, suggesting a direct stimulatory effect on hepatic ketogenesis. The data demonstrate that in normal humans the hyperketonemic effect of elevated plasma norepinephrine concentrations results from a combination of three factors: increased ketone body production from augmented FFA supply to the liver; accelerated hepatic ketogenesis; and modestly decreased metabolic clearance of ketone bodies. Acute insulin deficiency augments all these effects and results in progressive ketosis.
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PMID:Stimulatory effect of norepinephrine on ketogenesis in normal and insulin-deficient humans. 615 Jun 42

In isolated detrusor from guinea-pigs and rats substance P (SP) induced concentration-dependent phasic contractions. Rabbit detrusor strips responded to SP with an initial phasic and an ensuing tonic contraction. The concentration-response curve to SP in this preparation had a biphasic appearance. Eledoisin (E) caused contractile responses similar to those of SP when tested on the guinea-pig detrusor. Somatostatin was tested on the rabbit urinary bladder; it caused a concentration-dependent rise in basal tone, but no phasic contraction. The responses to SP and E were not affected by tetrodotoxin or physostigmine. They were only partly inhibited by high concentrations of atropine and the anticholinergic drug PR 197. Noradrenaline and isoprenaline caused a concentration-dependent inhibition of the peptide induced responses in guinea-pig bladder; at high concentrations in the amines this inhibition was almost complete. Indomethacin did not affect the SP induced contractions in the guinea-pig bladder, reduced the responses in the rabbit detrusor, but increased them in the rat bladder. Contractions elicited by SP and E were rapidly diminished or abolished after 30 min. treatment in a calcium-free medium. The responses were also inhibited by the calcium antagonist nifedipine. In guinea-pig preparations depolarized by potassium (127 mM) both SP and E caused a contractile response approximately 20% of that obtained in normal Tyrode solution. It is concluded that SP and E cause contraction of detrusor by a direct effect on the smooth muscle cells, and that this response is dependent on the extracellular calcium concentration. Prostaglandins may be involved in the SP-induced response of the rabbit detrusor.
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PMID:Contractile effects of some polypeptides on the isolated urinary bladder of guinea-pig, rabbit, and rat. 617 55

1. The effect of substance P on the phasic longitudinal contractions of the isolated rabbit ileum has been investigated. The contractions were recorded isotonically. Substance P in concentrations below those which cause tonic contraction (0.2-2 nM) increased the height of the phasic contractions in a concentration-dependent fashion without affecting their frequency (8-12/min).2. The effect of substance P was inhibited by verapamil, ouabain, noradrenaline, and isoprenaline, but was unaffected by tetrodotoxin, atropine, D-2-ala,5-metenkephalin, somatostatin, and vasoactive intestinal polypeptide.3. Tetraethylammonium, which blocks voltage-dependent K(+) channels, enhanced the phasic contractile activity of the rabbit ileum in a manner quite similar to substance P, but the maximal response to tetraethylammonium was larger than that to substance P.4. The effect of matched concentrations of substance P and tetraethylammonium, which enhanced the phasic contractions to a similar extent, was investigated at various concentrations of K(+), Na(+), Ca(2+) and Cl(-) in the bathing medium. Both substance P and tetraethylammonium lost their ability to enhance the phasic contractions when K(+) was omitted from the medium or when its concentration therein was increased by a factor of 4, or when the NaCl concentration was reduced to less than 10%. The relative increase in phasic contractile activity evoked by substance P was smaller than that evoked by tetraethylammonium when more than 90% of the Cl(-) was replaced with propionate.5. Noradrenaline, in a concentration which just abolished the spontaneous phasic contractions (200-300 nM), reduced the enhancing effect of substance P on the phasic activity by 40-50%, but did not influence the effect of tetraethylammonium.6. These results indicate that substance P enhances the phasic longitudinal contractions of the isolated rabbit ileum by a direct action on the smooth muscle cells and that this effect is brought about by facilitation of the myogenically controlled action potential discharges in the ileum. Circumstantial evidence suggests that the underlying ionic mechanism of action of substance P is a decrease in K(+) and Cl(-) conductances.
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PMID:An enquiry into the mechanism by which substance P facilitates the phasic longitudinal contractions of the rabbit ileum. 618 Jan 64

Norepinephrine, acetylcholine, and certain peptides are contained in mucosal nerves and have potent effects on transepithelial water and electrolyte fluxes. It is difficult to ascribe roles for these nerves as their sources are unknown. The present studies were undertaken to determine the origins of nerve fibers that are found in the mucosa of the guinea pig small intestine and which contain one of the following substances: vasoactive intestinal peptide, substance P, somatostatin, neuropeptide Y, cholecystokinin, or norepinephrine. Nerve fiber origins were ascertained by making lesions to sever pathways through which the nerves could reach the mucosa. The lesioning operations were homotopic autotransplants of short (2 cm) segments of intestine; myectomies, in which a 5-10-mm length of intestine was stripped of longitudinal muscle and myenteric plexus; and extrinsic denervation, in which nerves reaching the intestine through the mesentery were severed. The results of these studies, considered along with previously published work, led to the upcoming conclusions. Nerve fibers in the mucosa showing immunoreactivity for vasoactive intestinal peptide, somatostatin, cholecystokinin, and neuropeptide Y arise from cell bodies in the overlying submucous plexus. Substance P fibers arise in part from the overlying submucous plexus and in part from the overlying myenteric plexus. Mucosal norepinephrine fibers arise from extrinsic sympathetic ganglia. Enkephalin, gastrin-releasing peptide, and 5-hydroxytryptamine, which are in some enteric nerves, are not found in submucous nerve cells and few, if any, fibers containing these substances supply the mucosa. Thus, the mucosa receives a dense nerve supply, much of which arises locally from submucous ganglia.
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PMID:Origins of peptide and norepinephrine nerves in the mucosa of the guinea pig small intestine. 619 54

The role of the nerves in the hepato-duodenal ligament should be of special surgical interest, since these nerves are often injured in hepatic and biliary tract surgery. We have developed a microsurgical procedure for liver denervation. All visible nerves were resected after staining. Norepinephrine values in central liver tissue of denervated rats were only 18% of the corresponding values in innervated liver tissue, indicating an appreciable degree of sympathetic denervation. No detectable immunoreactivity of gastrin, cholecystokinin, vasoactive intestinal polypeptide, substance P, somatostatin or enkephalin were found within resected hepatic nerves. The described denervation procedure is simple and reproducible. It can be used to obtain additional information about the nervous regulation of various liver functions.
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PMID:A microsurgical method for denervation of the liver in the rat. 620 77


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