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)

Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [3H]substance P (IC50 = 3.3 +/- 1.8 x 10(-7) M) from guinea-pig bronchial tachykinin NK1 sites. The displacement of [125I]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 +/- 0.6 x 10(-6) M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.
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PMID:In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin. 755 7

1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.
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PMID:Neurogenic vasodilatation and plasma leakage in the skin. 945 75

We have used a combination of autoradiographic and immunohistochemical techniques to investigate the distribution of binding sites for substance P in relation to the distribution of substance P-immunoreactive nerve fibres and specific functional populations of neurons in the sympathetic ganglia of guinea-pigs. There was considerable heterogeneity in the density of binding sites for Bolton Hunter labelled 125I - substance P (BHSP). Binding sites were more dense in the prevertebral ganglia, such as the coeliac and inferior mesenteric ganglia, than in the paravertebral ganglia, such as the superior cervical or lumbar chain ganglia. The binding sites tended to be clumped within the ganglia. Within the prevertebral ganglia, they were associated predominantly with neurons projecting to the enteric plexuses. Many of these neurons contained somatostatin immunoreactivity. In the lumbar sympathetic chain ganglia, there was a weak association of binding sites with neurons containing immunoreactivity to vasoactive intestinal peptide. Overall, the density of binding sites matched the density of nerve fibres containing immunoreactivity to substance P in different ganglia. However, within particular ganglia, there was little, if any, correlation between the distribution of binding sites and nerve fibres containing substance P. Most of the binding sites in the ganglia had the pharmacological characteristics of NK1 receptors. Our results show that there is considerable heterogeneity in the expression of NK1 receptors in the sympathetic ganglia of guinea-pigs. However, given the relatively poor spatial correlation between the distribution of binding sites and potential sites of substance P release from intraganglionic nerve fibres, we suggest that substance P may diffuse for relatively large distances through the ganglia, with actions only on those neurons selectively expressing NK1 receptors.
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PMID:Differential distribution of substance P binding sites in guinea-pig sympathetic ganglia. 969 65

Simultaneous immunofluorescence labelling was used to investigate the patterns of colocalisation of the NK1 tachykinin receptor with other neuronal markers, and hence determine the functional classes of neuron that bear the NK1 receptor in the guinea-pig ileum. In the myenteric plexus, 85% of NK1 receptor-immunoreactive (NK1r-IR) nerve cells had nitric oxide synthase (NOS) immunoreactivity and the remaining 15% were immunoreactive for choline acetyltransferase (ChAT). Of the latter group, about 50% were immunoreactive for both neuropeptide Y (NPY) and somatostatin (SOM), and had the morphologies of secretomotor neurons. Many of the remaining ChAT neurons were immunoreactive for calbindin or tachykinins (TK), but not both. These calbindin immunoreactive neurons had Dogiel type II morphology. No NK1r-IR nerve cells in the myenteric plexus had serotonin or calretinin immunoreactivity. In the submucosal ganglia, 84% of NK1r-IR nerve cells had neuropeptide Y immunoreactivity and 16% were immunoreactive for TK. It is concluded that NK1r-IR occurs in five classes of neuron; namely, in the majority of NOS-immunoreactive inhibitory motor neurons, in ChAT/TK-immunoreactive excitatory neurons to the circular muscle, in all ChAT/NPY/SOM-immunoreactive secretomotor neurons, in a small proportion of ChAT/calbindin myenteric neurons, and in about 50% of ChAT/TK submucosal neurons.
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PMID:Identification of the populations of enteric neurons that have NK1 tachykinin receptors in the guinea-pig small intestine. 972 53

Sendide, a tachykinin NK1 receptor antagonist, was tested for antagonism against scratching, biting and licking responses elicited by intrathecal (i.t.) injections of various tachykinin receptor agonists, N-methyl-D-aspartate (NMDA), somatostatin and bombesin, in mice. Tachykinin NK1 receptor agonists, substance P, physalaemin and septide, produced a characteristic behavioural response, consisting of scratching, biting and licking. The substance P-induced response was reduced by small doses (0.0625-1.0 pmol) of sendide in a dose-dependent manner. The behavioural response elicited by other tachykinin NK1 receptor agonists, physalaemin and septide, was also reduced significantly by a small dose (1.0 pmol) of sendide. The inhibitory effect of sendide (1.0 pmol) was not affected by pretreatment with the opioid receptor antagonist, naloxone, at doses up to 4.0 mg/kg. Higher doses of sendide were needed to reduce the behavioural response to neurokinin A, a tachykinin NK2 receptor agonist, neurokinin B, a tachykinin NK3 receptor agonist and eledoisin, a tachykinin NK2/NK3 receptor agonist. Pretreatment with naloxone (2.0 mg/kg, i.p.) significantly antagonized sendide (1024 pmol)-induced inhibition of the behavioural responses to neurokinin A, neurokinin B and eledoisin. The behaviours elicited by i.t. injection of NMDA, somatostatin or bombesin were also reduced by a higher dose (1024 pmol) of sendide and this sendide effect was reversed by naloxone. These findings suggest that sendide at higher doses may possess opioid activity in addition to an antagonistic action at tachykinin NK1 receptors in the spinal cord.
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PMID:Opioid activity of sendide, a tachykinin NK1 receptor antagonist. 1022 61

Interstitial cells of Cajal (ICCs) are specialized cells of the gastrointestinal tract forming distinct populations depending on their location in the gut wall. Morphological observations and functional data have led to the hypothesis of two functions for the ICCs: (1) as pacemakers of the rhythmic activity; (2) as intermediaries in neural inputs to the muscle. The identification of specific receptors on the ICCs has represented an important step in the knowledge of these cells. Immunohistochemical labeling of these receptors provided information on both ICC morphology and contacts (particularly those with nerve endings) and on the functions of these cells. All ICC possess the Kit receptor, which represents the best tool to identify these cells under the light microscope. It has been demonstrated that this receptor is essential for ICC differentiation, and, by using mutant mice lacking the Kit-related gene, it has been possible to discriminate among all the ICC those with a primary role as pacemakers. The ileal ICC, in particular those at the deep muscular plexus, express the tachykinin receptor NK1 and a subtype of somatostatin receptors and contain nitric oxide synthase. All these data support a primary role of these ICC in neural transmission.
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PMID:Receptors in interstitial cells of Cajal: identification and possible physiological roles. 1060 92

Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 microM) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 microM) reduced by about 50% the metformin-evoked increase in 5-HT outflow (P<0.05). Metformin-evoked release was not affected by scopolamine + hexamethonium, propranolol, the 5-HT3 receptor antagonist dolasetron, naloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 microM), somatostatin (1 microM) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 microM) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with metformin could, thus, be produced by the release of 5-HT and other neurotransmitter substances within the duodenal mucosa.
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PMID:Effects of metformin on intestinal 5-hydroxytryptamine (5-HT) release and on 5-HT3 receptors. 1065 Nov 52

Information about the expression of neuropeptide receptors is limited in human peripheral tissues, such as the gastrointestinal tract, as compared to the brain. A detailed evaluation of binding sites for gastrin-releasing peptide (GRP), neuropeptide Y, vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin/cholecystokinin, neurotensin, substance P and somatostatin was therefore undertaken in human colon using in vitro receptor autoradiography and subtype characterization with receptor-selective ligands. GRP receptors, Y2 receptors, PACAP type1-receptors, cholecystokinin-A receptors, neurotensinl and sst2 receptors were abundantly expressed in the myenteric plexus. Y2, neurotensinl and sst2 receptors were also strongly expressed in the submucosal plexus. Furthermore, expression of GRP receptors, neurokinin (NK)1 receptors, VIP type2-receptors and sst2 receptors was found in the mucosa-directed margin of the circular smooth muscle where the interstitial cells of Cajal are located. A variable and complementary expression of GRP receptors, VIP/PACAP receptors, Y2 neurotensinl, NK1 and somatostatin receptors was found in the circular and longitudinal smooth muscle. NK1 and Y1 receptors were often detected in arteries and veins, while VIP/PACAP and sst2 receptors were found in lymphoid follicles. Y2, VIP type, and sst2 receptors were present in the colonic mucosa. Y2 was strongly expressed in the muscularis mucosae. This study shows that neuropeptide receptors are expressed in high amounts and in highly specific patterns in distinct targets in the human colon, suggesting a major physiological role for these peptides. The data represent the molecular basis to investigate the regulation by neuropeptides of colonic functions and to develop neuropeptide drugs aimed at interacting with these receptors in colonic diseases, such as Hirschsprung's and Crohn's diseases.
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PMID:Localization and characterization of neuropeptide receptors in human colon. 1168 16

Parvalbumin-containing fast-spiking interneurons in the cerebral cortex exhibit widespread electrical coupling, as do somatostatin-containing low-threshold spiking interneurons. Besides the classical neurotransmitter gamma-aminobutyric acid, these cortical interneurons may also release various neuropeptides including substance P (SP), as well as the freely diffusible messenger nitric oxide (NO). To investigate whether these two networks of interneurons might interact via these nonclassical messengers, we performed immunocytochemistry for SP and NO signaling pathways in rat somatic sensory cortex. SP was found in a subset of parvalbumin-positive cells concentrated in layers IV and V, whereas its receptor, NK1, was found in a subset of somatostatin-containing neurons (and also, at much lower levels, in a disjoint subset of parvalbumin-containing neurons). Only 4% of SP-containing axon terminals were apposed to NK1-positive dendrites, suggesting that in the cerebral cortex, SP may act predominantly as a paracrine neuromediator. Nitric oxide synthase-I (NOS-I), the synthetic enzyme for NO, was found almost exclusively in NK1-positive neurons; 95% of intensely somatostatin/NK1-positive neurons were also positive for NOS-I, and 94% of NOS-positive neurons were also positive for NK1. Immunoreactivity for soluble guanylyl cyclase (the NO receptor) was at high levels in the apical dendrites of layer V pyramidal neurons and in parvalbumin/SP-positive neurons. These data point to a novel reciprocal chemical interaction between two inhibitory networks in the rat neocortex.
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PMID:Substance P and nitric oxide signaling in cerebral cortex: anatomical evidence for reciprocal signaling between two classes of interneurons. 1174 51

Synaptic terminals in the nucleus of the solitary tract (NTS) from axons originating in the central nucleus of the amygdala (CeA) are known to contain gamma-aminobutyric acid (GABA) immunoreactivity. Here, we have investigated whether such projections contain neuropeptides as putative co-transmitters. Somata in the medial and lateral CeA that were retrogradely labelled with cholera toxin B (CTb) injected into the commissural NTS were found to be immunoreactive for GABA, somatostatin (SOM), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS). Subpopulations of fibres in the NTS that were anterogradely labelled with biotin dextran amine (BDA) injected into the CeA and examined using both fluorescence and electron microscopy appeared to colocalise somatostatin, but not other neuropeptides. Their varicosities were observed in proximity to NTS neurones that were immunoreactive for the somatostatin receptor sst2A subtype, substance P (SP) NK1 receptor, and the GABAA receptor alpha3, beta1 and gamma2 subunits. This morphological evidence is consistent with the possibility of GABA-somatostatin co-transmission at synapses of some of the CeA projection neurones to NTS that might inhibit cardiovascular reflex responses in response to fear or emotion-related stimuli.
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PMID:Evidence for peptide co-transmission in retrograde- and anterograde-labelled central nucleus of amygdala neurones projecting to NTS. 1214 35


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