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)

Receptors for the main neural (acetylcholine), hormonal (gastrin) and paracrine (histamine) secretory stimulants and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of histamine is mediated via an increase in adenylate cyclase activity, whereas the effect of acetylcholine and gastrin are mediated via an increase in cytosolic levels of calcium. Strong synergism between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways. Acetylcholine and gastrin are also capable of releasing histamine from the gastric mucosa, probably from ECL cells. The inhibitory effects of somatostatin and prostaglandin E on acid secretion are mediated by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, ultimately responsible for acid secretion. The intramural neural and paracrine pathways involved in the regulation of gastrin secretion in the antrum and acid secretion in the fundus have also been identified. Of prime importance is the somatostatin cell, which exerts a paracrine restraint on gastrin secretion and acid secretion. Elimination of this restraint or disinhibition is one of the mechanisms by which the stimulatory influence of cholinergic neurons is exerted on gastrin and parietal cells. Gastrin secretion is regulated by a cholinergic neuron that causes inhibition of somatostatin secretion and thus stimulation of gastrin secretion (disinhibition) and a noncholinergic neuron that causes direct stimulation of gastrin secretion by releasing the neurotransmitter, bombesin (or gastrin-releasing peptide). Acid secretion is regulated by a cholinergic neuron that causes direct stimulation of the parietal cell and indirect stimulation by decreasing somatostatin secretion, thus eliminating its inhibitory effect on the parietal cell (disinhibition). In addition, a regulatory feedback mechanism exists whereby intraluminal acidification stimulates somatostatin secretion, which in turn attenuates acid secretion. Gastric acid secretion may also be regulated by one or more intestinal inhibitory hormones, the most likely candidates being secretin, intestinal somatostatin, and neurotensin. Enterogastrone activity probably reflects the combined effect of all these hormones. Precise information on receptors and signal transduction mechanisms as well as on intramural neural and paracrine regulatory pathways has led to the development of new drugs capable of inhibiting acid secretion. These include antagonists that interact with stimulatory receptors (histamine H2-receptor antagonists, muscarinic receptor antagonists, and gastrin receptor antagonists), agonists that interact with inhibitory receptors (somatostatin and prostaglandin E analogues), and irreversible inhibitors of the luminal enzyme, H+K(+)-ATPase.
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PMID:Control of acid secretion. 169 38

This study deals with the synaptology, morphologically identified postsynaptic targets, and origin of somatostatin (SOM) fibers in the rat lateral septal area (LSA) with special reference to those forming pericellular baskets. Septal vibratome sections were immunostained for SOM-14 in 3 experimental groups: control animals, rats subjected to a chronic transection of the ascending afferents to the septum, and animals with acute fimbria-fornix lesion. Light microscopy revealed that the SOM-immunoreactive fibers form pericellular baskets predominantly in the intermediate and ventral parts of the caudal half of the LSA. Electron microscopic analysis showed that the somatospiny neurons are postsynaptic targets of these pericellular baskets. Eight days after a unilateral cut placed at the ventral border of the septum, virtually all SOM-immunoreactive axon terminals disappeared from the ipsilateral intermediate and ventral LSA, and they were substantially reduced in the dorsal LSA. However, in these rats SOM-positive neurons could be observed in the LSA on the lesioned, but not on the contralateral side. Furthermore, on the lesion side of the anterior periventricular hypothalamus an increase was detected both in the number and the intensity of immunostaining of SOM-positive neurons. Thirty-six h following a unilateral transection of the fimbria-fornix, the SOM-immunoreactive axon terminals in the LSA remained intact; only immunonegative degenerated hippocamposeptal boutons were detected forming synaptic contacts with somatospiny neurons. Axosomatic synapses of SOM-positive boutons regularly appeared at the neck of somatic spines which were postsynaptic to degenerated hippocamposeptal fibers. The results indicate that the septal SOM fibers are of multiple origin. Those forming pericellular baskets in the LSA originate in ventral extraseptal, probably periventricular hypothalamic areas. SOM fibers scattered in the dorsal LSA are most likely processes of local SOM neurons. The accumulation of immunoreactive SOM in some cells of the undercut septum is a sign of axonal lesion, indicating that these neurons project outside the septum. The SOM innervation of somatospiny neurons which also receive hippocampal input and have been reported to contain gamma-aminobutyric acid (GABA) may be a morphological substrate of the SOM-related disinhibition in the LSA.
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PMID:Synaptology and origin of somatostatin fibers in the rat lateral septal area: convergent somatostatinergic and hippocampal inputs of somatospiny neurons. 172 20

The presence of acid in the lumen of the gastric fundus induces release of somatostatin close to the parietal cells; this acts to attenuate acid secretion in response to secretagogues, such as histamine and gastrin. The release of somatostatin within the stomach is further regulated by the activity of cholinergic neurons that inhibit somatostatin release and thus augment acid secretion (disinhibition), and noncholinergic (bombesin) neurons that stimulate somatostatin release and thus attenuate acid secretion. The influence of these neurons and the participation of somatostatin as a paracrine regulator of acid secretion has been probed and validated by the use of selective antagonists (atropine and a bombesin antagonist), somatostatin antiserum and pertussis toxin. Similar mechanisms exist in the distal antral segment of the stomach for the paracrine regulation of gastrin release by somatostatin.
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PMID:Gastric somatostatin: a paracrine regulator of acid secretion. 197 9

The pattern of TSH secretion in man in pulsatile in addition to the well known circadian variation. The mechanism triggering TSH pulses remains unclear to date. Infusions of somatostatin or dopamine rapidly lowering basal TSH levels without suppressing the pulsatile pattern suggest that an episodic disinhibition exerted by a physiological inhibitor is not a likely cause. On the same basis, thyroid hormones do not appear to be candidates, since they similarly inhibit basal TSH levels after a time lag of several hours but again do not suppress pulsatile release of the hormone. In contrast, bolus injections of dexamethasone completely abolish pulsatile release of TSH for several hours despite a normal sensitivity of the pituitary to exogenous TRH, suggesting a hypothalamic action of the drug. The hypothesis that pulsatile TSH release might be governed by a pulsatile mode of a hypothalamic stimulator is supported by the observation that an infusion of nifedipine, a calcium channel blocker, which in vitro selectively inhibits the TRH effect on TSH but not prolactin secretion, exerts a comparable effect when it is infused in vivo.
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PMID:Physiological regulation of thyrotropin. 249 28

During the course of studies of the effects of pantethine, a cysteamine precursor known to deplete tissue concentration of immunoreactive somatostatin, we observed that the subject rats continued to eat despite marked distension of the stomach. To determine whether this effect was caused by drug-altered food intake, we have measured food and water intake in pantethine-injected rats in the fed and fasting state. In three separate experiments, rats allowed free access to food until the morning of study showed significant increased food intake accompanied by an increased stomach content (at 4 hr) of both food and water following the IP injection of pantethine. In one experiment, intake at 3 hours was 0.60 g/100 g b.wt. (pantethine dose 0.74 g/kg b.wt.) and 0.64 g/100 g b.wt. (pantethine dose 1.47 g/kg b.wt.) compared with 0.24 g/100 g b.wt. in saline-treated animals (p less than 0.05). In contrast, pantethine, 1.47 g/kg b.wt., when administered to overnight-fasted rats, significantly inhibited food intake (3-hr intake 1.54 +/- 0.16 g/100 g b.wt. in rats injected with pantethine 1.47 g/kg b.wt. as compared with 3.3 +/- 0.21 g/100 g b.wt. in saline-injected controls). The intake-stimulating effect of pantethine in ad lib-fed rats was not demonstrable when the drug was administered shortly before the "lights out"-induced feeding at night. These findings indicate that pantethine, a cysteamine precursor, stimulates food intake in satiated rats, depending upon the stage of circadian rhythm, but is inhibitory to intake in fasted animals. We postulate that the effects are mediated directly or indirectly through the disinhibition of central appetite-regulating somatostatinergic pathways but, since cysteamine also inhibits dopamine-beta-hydroxylase, an effect on depletion of appetite-regulating central catecholamines cannot be excluded.
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PMID:Pantethine, a somatostatin depleting agent, increases food intake in rats. 258 1

In addition to its classical growth hormone (GH) inhibiting action, somatostatin (SRIF) inhibits prolactin (PRL) secretion in man and rat under specific endocrine conditions. Furthermore, SRIF counteracts the thyrotropin releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated prolactin release from rat adenohypophysis in vitro. Two criteria are needed to demonstrate a physiological role of SRIF in PRL control: specific receptors must be present on prolactin secreting cells, and antagonization of endogenous SRIF must affect PRL secretion in vitro. In fact [125I]N--Tyr--SRIF binds to membranes not only of human GH-secreting adenomas, but also of prolactinomas. Specific binding characteristics are comparable in both cell types, but the density of sites in PRL-secreting adenomas is only one-quarter that in GH-secreting adenomas. In contrast, non-PRL-secreting chromophobe adenomas are devoid of specific binding. On the other hand, administration of SRIF antisera (SRIF-AS) affects both GH and PRL secretion in starved rats (a model in which pulsatile GH secretion is abolished); a marked increase in PRL plasma levels occurs, but the needed SRIF-AS concentration is higher than that for GH disinhibition. This demonstrates that endogenous SRIF may exert a negative control over PRL secretion, although lactotroph cells appear less sensitive to SRIF than somatotrophs. Since the apparent affinity of SRIF binding sites is similar on both GH and PRL secreting cells, at least in human tumor tissues, a lower density of SRIF receptors on PRL cells could account for this reduced responsiveness. Alternatively, different coupling mechanisms may be involved in the two cell types.
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PMID:Somatostatin and regulation of prolactin secretion. 287 80

The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus was developed to study changes in structure and function that occur as a result of repetitive seizures. Hippocampal granule cell seizure activity caused a persistent loss of recurrent inhibition and irreversibly damaged adjacent interneurons. Immunocytochemical staining revealed unexpectedly that gamma-aminobutyric acid (GABA)-containing neurons, thought to mediate inhibition in this region and predicted to be damaged by seizures, had survived. In contrast, there was a nearly complete loss of adjacent somatostatin-containing interneurons and mossy cells that may normally activate inhibitory neurons. These results suggest that the seizure-induced loss of a basket cell-activating system, rather than a loss of inhibitory basket cells themselves, may cause disinhibition and thereby play a role in the pathophysiology and pathology of the epileptic state.
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PMID:Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. 287 52

This paper reviews the central consequences of local application of capsaicin to one nerve in adult animals. 1) Marked chemical changes occur in the central terminals of C fibres. These include depletion of the enzyme FRAP and the peptides SP, CCK, somatostatin, CGRP and an increase of VIP. Maximal depletions occur if the nerve is soaked with capsaicin solutions with a concentration higher than 3 mM. The depletion begins by 7 days and is complete by 11. Recovery begins at about 110 days and is largely complete by 200. Our studies have concentrated on the effects of 40 mM capsaicin examined 14 days after the application. 2) Capsaicin treatment of a peripheral nerve decreased the ability of C fibres in that nerve to excite or to inhibit spinal cord cells. It produces a marked expansion of receptive fields of some cells in the dorsal horn which respond to A fibre stimulation. It is proposed that this change is not due to anatomical changes but to disinhibition. A further example of receptive field expansion is seen after treatment of the mouse infraorbital nerve which defocuses the normally precise projection of individual whiskers onto single cells in the barrel field of the somatosensory cortex. 3) Behavioural consequences follow the treatment of one adult nerve with capsaicin. In the area subserved by the treated nerve, there is a raised threshold to response to chemical and thermal stimuli, no change in the response to mechanical stimuli and an increase of autotomy following nerve section. 4) The aim of the experiments was to determine the role of C fibres in producing the changes seen in spinal cord following peripheral nerve section. Capsaicin treatment of nerve imitates the central effect of complete nerve section in certain important ways. Both result in a marked expansion of the receptive field of some cells. The effect is produced by a change of chemical transport. The results show that C fibres influence the connection of A fibres onto spinal cord cells.
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PMID:The central consequences of the application of capsaicin to one peripheral nerve in adult rat. 331 May 19

The role of endogenous somatostatin in the pathogenesis of duodenal was investigated in the present study by using the cysteamine animal model of the disease. Our previous studies showed a rapid and multiorgan depletion of somatostatin immunoreactivity (SIR) in rats given a single dose of duodenal ulcerogen cysteamine. We now determined whether acetylcholinergic and dopaminergic modulation (both known to influence the development of duodenal ulcer) are accompanied by modification of cysteamine-induced SIR depletion in rat organs. Vagotomy performed either 1 or 18 h before cysteamine administration did not interfere with the chemically induced SIR decrease in pancreas, gastric and duodenal mucosa. Vagal denervation alone had no marked influence on SIR levels but if combined with cysteamine, the SIR depletion in the stomach was significantly more pronounced than after the duodenal ulcerogen alone. Pretreatment with the dopamine agonists bromocriptine or lergotrile (known to prevent the chemically induced duodenal ulcers) did not influence the SIR depletion by cysteamine. Thus cysteamine depletes endogenous somatostatin in peripheral organs (e.g., stomach, duodenum, pancreas) by mechanisms independent of both vagus nerve and dopamine agonists. A role of central somatostatin depletion leading to disinhibition of vagus is also considered in the pathogenesis of experimental duodenal ulcer.
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PMID:Somatostatin depletion of the gut and pancreas induced by cysteamine is not prevented by vagotomy or by dopamine agonists. 613 42

Neurons of the supramammillary nucleus are known to fire phase-locked to hippocampal theta rhythm. Stimulation of this area induces theta activity in the hippocampus via the medial septum and facilitates perforant pathway stimulation-evoked population spikes in the dentate gyrus even if the medial septum is inactivated. This latter effect was suggested to be due to a direct inhibitory input from the supramammilary nucleus to hippocampal nonpyramidal cells resulting in disinhibition. In the present study, using anterograde tracing with Phaseolus vulgaris leucoagglutinin, we aimed to identify the types of neurons innervated by the supramammillary projection in the dentate gyrus and Ammons horn, with particular attention to the presumed postsynaptic inhibitory neurons, which may mediate the proposed disinhibitory action. Double-immunostaining for the tracer and different neuropeptides (somatostatin, cholecystokinin, neuropeptide Y) or calcium binding proteins (calretinin, parvalbumin, calbindin D28K) present in different subpopulations of interneurons revealed no multiple contacts between supramammillary afferents and labeled inhibitory cells at the light microscopic level. Furthermore, postembedding immunostaining of electron microscopic sections for GABA demonstrated that none of the 68 PHAL-labeled supramammillary boutons examined and none of their postsynaptic targets were immunoreactive for the inhibitory neurotransmitter. We conclude, therefore, that most if not all postsynaptic targets of the supramammillary projection are principal cells both in the dentate gyrus and in the CA2-CA3a subfields. This suggests that a mechanism other than disinhibition is responsible for the facilitatory effect of this pathway on hippocampal evoked activity.
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PMID:Principal cells are the postsynaptic targets of supramammillary afferents in the hippocampus of the rat. 753 Oct 93


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