Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that a subset of enteric neurons is glucoresponsive and expresses ATP-sensitive K(+) (K(ATP)) channels. The immunoreactivities of the inwardly rectifying K(+) channel 6.2 (Kir6.2) and the sulfonylurea receptor (SUR), now renamed SUR1, subunits of pancreatic beta-cell K(ATP) channels, were detected on cholinergic neurons in the guinea pig ileum, many of which were identified as sensory by their costorage of substance P and/or calbindin. Glucoresponsive neurons were distinguished in the myenteric plexus because of the hyperpolarization and decrease in membrane input resistance that were observed in response to removal of extracellular glucose. The effects of no-glucose were reversed on the reintroduction of glucose or by the K(ATP) channel inhibitor tolbutamide. No reversal of the hyperpolarization was observed when D- mannoheptulose, a hexokinase inhibitor, was present on the reintroduction of glucose. Application of the K(ATP) channel opener diazoxide or the ob gene product leptin mimicked the effect of glucose removal in a reversible manner; moreover, hyperpolarizations evoked by either agent were inhibited by tolbutamide. Glucoresponsive neurons displayed leptin receptor immunoreactivity, which was widespread in both enteric plexuses. Superfusion of diazoxide inhibited fast synaptic activity in myenteric neurons, via activation of presynaptic K(ATP) channels. Diazoxide also produced a decrease in colonic motility. These experiments demonstrate for the first time the presence of glucoresponsive neurons in the gut. We propose that the glucose-induced excitation of these neurons be mediated by inhibition of K(ATP) channels. The results support the idea that enteric K(ATP) channels play a role in glucose-evoked reflexes.
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PMID:Identification and characterization of glucoresponsive neurons in the enteric nervous system. 1057 28

Vagal afferent nerve fibres are involved in the transmission to the central nervous system of information relating to food intake and immune reactions. Leptin is involved in the control of food intake and has specific receptors in afferent vagal neurones. To investigate the role of these receptors, we studied the effects of leptin on single vagal afferent activities from intestinal mechanoreceptors in anaesthetized cats. The activity of 35 intestinal vagal mechanoreceptors was recorded by means of glass microelectrodes implanted in the nodose ganglion. Leptin (10 microg), administered into the artery irrigating the upper part of the intestine, induced activation in 17 units (P < 0.001), inhibition in 8 units (P < 0.05), and had no effect on 10 units. The excitatory effects of leptin were blocked by the endogenous interleukine-1beta receptor antagonist, (Il-1ra, 250 microg, I.A.). Cholecystokinin (CCK, 10 microg, I.A.) induced an activatory response only in the two types of units which were responsive to leptin alone. When leptin was administered after CCK, its excitatory effects were enhanced and its inhibitory effects were blocked, whereas it had no effect on the units which were not affected by leptin alone. The interactions between leptin and CCK are specific ones, since other substances (phenylbiguanide, a serotoninergic agonist; substance P) known to activate the mechanoreceptors did not modify the effects of leptin. These results indicate that leptin appears to play a role in the control of immune responses and food intake via intestinal vagal afferent nerve fibres and that there is a functional link between leptin and Il-1beta.
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PMID:Effects of leptin on cat intestinal vagal mechanoreceptors. 1220 99

Vagal afferents are extensively distributed in the digestive tract from the oesophagus to the colon. They are involved in the reflex control of normal gastrointestinal (GI) tract function (e.g. secretion and motility) as well as reflexes more characteristic of diseases such as functional dyspepsia and gastroesophageal reflux disease (e.g. vomiting, disordered lower esophageal sphincter relaxation and gastric accommodation). They are also implicated in signalling non-painful sensations (e.g. nausea and early satiety) associated with disease. A variety of receptors has been identified on vagal afferents, which can either enhance (e.g. 5-HT3, CCK1, VR1 and NK1 receptors) or reduce (e.g. ghrelin, leptin, k-opioid and GABAB receptors) activity, offering a range of potential therapeutic targets. Commonly used laboratory species (e.g. rat and mouse) lack an emetic reflex, and the implications of this for models of upper GI disorders have been explored in the light of expanding knowledge of the neuropharmacology of the emetic reflex implicating glutamate, prostanoids, cannabinoids and substance P. Additional pathophysiological roles for vagal afferents (e.g. in thermoregulation, arousal and fatigue) are being investigated, raising the intriguing possibility of the vagus as a target in non-GI disorders.
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PMID:Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. 1248 26

The neuropeptide leptin has been shown to selectively modulate rat chorda tympani (CT) responses to sweet tastants. To explore whether other neuropeptides can modulate such responses, rat whole nerve CT responses to NaCl, HCl, quinine HCl, and sucrose were measured while administering cholecystokinin-8 (CCK-8), substance P(4-11) (SP(4-11)), or calcitonin gene-related peptide (CGRP). To avoid possible confounding effects on CT responses that take long times to develop, such as those that arise from intraperitoneal injections, we investigated the effects of the above peptides injected into the ipsilateral lingual artery (LA) on CT nerve responses during the initial seconds after a tastant was placed on the tongue. We found that CT responses to NaCl and HCl were increased by CCK-8 and decreased by CGRP. SP(4-11) had no noticeable effect. Peptide-induced CT responses to quinine HCl or sucrose were too small to accurately detect. These data suggest that at short latencies, after local infusion via the LA, neuropeptides can alter CT responses in a peptide-specific manner.
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PMID:Neuropeptides modulate rat chorda tympani responses. 1273 81

The immune system and the nervous system maintain extensive communication, including 'hardwiring' of sympathetic and parasympathetic nerves to lymphoid organs. Neurotransmitters such as acetylcholine, norepinephrine, vasoactive intestinal peptide, substance P and histamine modulate immune activity. Neuroendocrine hormones such as corticotropin-releasing factor, leptin and alpha-melanocyte stimulating hormone regulate cytokine balance. The immune system modulates brain activity, including body temperature, sleep and feeding behavior. Molecules such as the major histocompatibility complex not only direct T cells to immunogenic molecules held in its cleft but also modulate development of neuronal connections. Neurobiologists and immunologists are exploring common ideas like the synapse to understand properties such as memory that are shared in these two systems.
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PMID:Elaborate interactions between the immune and nervous systems. 1528 54

Nerves have been identified in bone. Their function has recently become the focus of intense study. Metabolic control of bone is influenced by the nervous system. Potential transmitters of this influence include glutamate, calcitonin gene-related protein (CGRP), substance P, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), leptin, and catecholamines. Disorders of nerves - central or peripheral--can have substantial influence on bone health and repair. Specifically considered are the potential neural influences at work in such conditions as osteoporosis, fracture healing, Charcot osteoarthropathy, musculoskeletal pain syndromes, heterotopic ossification, skeletal growth and development, and obesity-related increased bone density. In this article, we review the current state of experimental and clinical evidence implicating the role of nervous tissue in regulating bone biology and discuss the current understanding of molecular signaling between nervous and osseus tissue in the homeostatic maintenance of the skeleton.
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PMID:Bone and brain: a review of neural, hormonal, and musculoskeletal connections. 1529 19

Many neuropeptides regulate feeding and arousal; the ventral tegmental area (VTA) is likely to be one site where they act. We used whole-cell patch-clamp and single-unit extracellular recordings to examine the effects of such neuropeptides on the activity of VTA neurons. Substance P (SP; 300 nM) increased the firing rate of the majority of VTA dopaminergic and gamma-aminobutyric acid (GABA)ergic neurons, and induced oscillations in two dopaminergic cells. Corticotropin-releasing factor (CRF; 200 nM) excited the majority of VTA cells directly, whereas neuropeptide Y (NPY; 300 nM) directly inhibited a subset of dopaminergic and GABAergic cells. Consecutive application of several neuropeptides revealed that all the neurons were excited by at least one of the excitatory neuropeptides SP, CRF or/and orexins. Alpha-melanocyte-stimulating hormone had no effect on dopaminergic cells (at concentrations of 500 nM and 1 microM) and affected only a small proportion of GABAergic neurons. Ghrelin (500 nM), agouti-related peptide (1 microM); cocaine and amphetamine-related transcript (500 nM) and leptin (500 nM and 1 microM) did not modulate the firing rate and membrane potential of VTA neurons. Single-cell reverse transcription polymerase chain reaction analysis showed that all NPY receptors were present in VTA neurons, and all but one cell expressed NPY and/or at least one NPY receptor. CRF was expressed in 70% of dopaminergic VTA cells; the expression of CRF receptor 2 was more abundant than that of receptor 1. These findings suggest a link between the ability of neuropeptides to promote arousal and their action on VTA neurons.
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PMID:Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat. 1681 70

Overlapping neural, hormonal, and paracrine pathways finely regulate gastric acid secretion. In rats and guinea pigs, most of the intrinsic neural innervation to the gastric mucosa originates in the myenteric plexus. In contrast, human stomachs have a clearly defined submucosal plexus that contains a variety of transmitters including nitric oxide, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), substance P, and calcitonin gene-related peptide (CGRP). Although GRP is known to participate in meal-stimulated acid secretion by releasing gastrin in a variety of laboratory animals, recent studies were unable to demonstrate a role for endogenous GRP in meal-stimulated gastrin secretion in humans. Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the secretin-glucagon-VIP family, has been localized to gastric mucosal neurons and may participate in vagally mediated acid secretion. Two novel peptides, ghrelin and leptin, have been localized to the stomach. Peripheral administration of ghrelin stimulates and of leptin inhibits acid secretion. The binding of secretagogues to parietal cells generates changes in second messengers that regulate the translocation and activation of the proton pump, HK-ATPase. In resting cells, HK-ATPase is contained within cytoplasmic tubulovesicles in an inactive form. At stimulation, the tubulovesicles fuse with the apical canaliculi and the HK-ATPase is incorporated into the apical membrane where it actively pumps H ions in exchange for K. Acute infection with Helicobacter pylori results in hypochlorhydria, whereas chronic infection can cause either hypo- or hyperchlorhydria, depending on the distribution of the infection and the degree of corpus gastritis. Recent studies suggest that inflammatory cytokines, produced in response to the organism, can play a role in the perturbations in acid and gastrin secretion induced by H. pylori.
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PMID:Gastric secretion. 1703 42

This paper centers on some whole-istic organizational and functional aspects of hepatic Schistosoma mansoni granuloma, which is an extremely complex system. First, it structurally develops a collagenic topology, originated bidirectionally from an inward and outward assembly of growth units. Inward growth appears to be originated from myofibroblasts derived from small portal vessel around intravascular entrapped eggs, while outward growth arises from hepatic stellate cells. The auto-assembly of the growth units defines the three-dimensional scaffold of the schistosome granulomas. The granuloma surface irregularity and its border presented fractal dimension equal to 1.58. Second, it is internally regulated by intricate networks of immuneneuroendocrine stimuli orchestrated by leptin and leptin receptors, substance P and Vasoactive intestinal peptide. Third, it can reach the population of +/- 40,000 cells and presents an autopoietic component evidenced by internal proliferation (Ki-67+ Cells), and by expression of c-Kit+ Cells, leptin and leptin receptor (Ob-R), granulocyte-colony stimulating factor (G-CSF-R), and erythropoietin (Epo-R) receptors. Fourth, the granulomas cells are intimately connected by pan-cadherins, occludin and connexin-43, building a state of closing (granuloma closure). In conclusion, the granuloma is characterized by transitory stages in such a way that its organized structure emerges as a global property which is greater than the sum of actions of its individual cells and extracellular matrix components.
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PMID:Four whole-istic aspects of schistosome granuloma biology: fractal arrangement, internal regulation, autopoietic component and closure. 1730 73

Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro proangiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis.
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PMID:Nonclassic endogenous novel [corrected] regulators of angiogenesis. 1754 Sep 6


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