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

The activity of septo-hippocampal neurones is affected by the action on cholinergic perikarya in the septum of a variety of putative neurotransmitters, including substance P and beta-endorphin. (The latter is released in the septal region from neurones which originate in the medial basal hypothalamus.) It has also been reported that two other neuropeptides, corticotropin (ACTH1-24) and alpha-melanotropin (alpha-MSH), affect acetylcholine turnover in septo-hippocampal neurones in a manner that is not blocked by transection of the afferents to the hippocampus, from which it has been inferred that the neurotransmitters act directly on the hippocampus. We now describe experiments with corticotropin which show that the effect is rather the influence on septo-hippocampal cholinergic neurones of peptidergic neurones within the septum.
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PMID:Corticotropin regulates transsynaptically the activity of septo-hippocampal cholinergic neurones. 625 48

In the present work we studied the interaction of alpha-MSH and substance P neuropeptides with gangliosides using lipid monolayers, fluorescence spectroscopy, and differential scanning calorimetry techniques. The positively charged weak amphiphilic neuropeptides did not show surface activity in the range of concentrations tested (0.1-0.3 muM), but they were preferentially able to penetrate monolayers formed by acidic lipids, showing the best interaction with the more complex gangliosides. The general order of interaction found for both peptides is GTIh > GDIa = GMI > DLPA > sulphatide. Neither neuropeptide interacted with phosphatidylcholine monolayers above 10 mN.m-1. The binding of alpha-MSH to GMI micelles followed by changes in the fluorescence of its tryptophan residue takes place with an increase in the hydrophobic environment of the neuropeptide. An apparent dissociation constant of 13 muM was estimated for this process. Similar result was found with GMI:DMPC vesicles (1:10 molar ratio). The thermotropic profile of GMI micelles is modified in the presence of the neuropeptides. The calorimetric enthalpy of GMI transition increased 21% and 37% in the presence of alpha-MSH and substance P, respectively. Both neuropeptides induced the same increment in the transition temperature Tm from 19 to 20.5 degrees C. The basic physicochemical studies herein indicated that both positively charged neuropeptides, alpha-MSH and substance P, interact with interfaces containing gangliosides in a mainly electrostatic form, whereas the hydrophobic interaction seems to play a secondary role.
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PMID:Interaction of alpha-MSH and substance P with interfaces containing gangliosides. 880 33

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 and Val19 of the natural peptide were replaced by phenylalanyl and tyrosyl residues: [Phe13, Tyr19]-MCH. The peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and polyhipe PA 500 and PEG-PS resins. The linear MCH peptides with either acetamidomethyl-protected or free cysteinyl residues were purified to homogeneity and cyclized by iodine oxidation, yielding the final product with the correct molecular weight of 2434.61. Radioiodination of the C-terminal tyrosine was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and by high-pressure liquid chromatography. The resulting [125I]-[Phe13, Tyr19]-MCH tracer was the first radiolabelled MCH peptide suitable for radioreceptor assay: saturation binding analysis using mouse G4F-7 melanoma cells demonstrated the presence of 1090 MCH receptors per cell. The dissociation constant (KD) was 1.18 x 10(-10) M, indicating high-affinity MCH receptors on these cells. MCH receptors were also found in other cell lines such as mouse B16-F1 and G4F and human RE melanoma cells as well as in PC12 and COS-7 cells. Competition binding analyses with a number of other peptides such as alpha-MSH, neuropeptide Y, substance P and pituitary adenylate cyclase activating peptide, demonstrated that the binding to the MCH receptor is specific. Atrial natriuretic factor was found to be a weak competitor of MCH, indicating topological similarities between MCH and ANF when interacting with MCH receptors.
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PMID:Synthesis and iodination of human (phenylalanine 13, tyrosine 19) melanin-concentrating hormone for radioreceptor assay. 922 84

Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which contain chelators for the radioisotopes 111In, 86Y, 90Y, 67Ga, 68Ga and 64Cu or for 99mTc and 188Re. and were labelled with the halogens 123I and 18F. Radiolabeled analogs of &alpha-melanocyte-stimulating hormone (&alpha-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP) and gastrin/cholecystokinin (CCK) are also being developed, evaluated in vitro and in vivo and tested for clinical application. This review focuses on the expression in tumors and the regulation of receptors for these neuropeptides as well as the development of novel chelator-peptide conjugates suitable for in vivo scintigraphy or internal radiotherapy. The state of the art of radiopeptide pharmaceuticals is illustrated with four SRIF analogs, modified with the macrocyclic chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA): [D-Phe1]-octreotide (DOTAOC), [D-Phe1, Tyr3]-octreotide (DOTATOC), vapreotide (DOTAVAP) and lanreotide (DOTALAN). DOTA is almost a universal chelator capable of strongly encapsulating hard metals such as 111In and 67Ga for Single Photon Emission Tomography (SPET), 68Ga, 86Y and 64Cu for Positron Emission Tomography (PET) as well as 90Y for receptor-mediated radionuclide therapy and radiolanthanides which exhibit different interesting decay schemes. From biodistribution studies in experimental animals and from clinical data it is concluded that DOTATOC is currently the most suitable SRIF radiopeptide with the best potential in the clinic.
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PMID:Receptor targeting for tumor localisation and therapy with radiopeptides. 1091 Oct 25

Several prostaglandin analogues used for glaucoma treatment cause increased pigmentation of the iris. The purpose of the present study was investigate whether latanoprost, a PGF(2 alpha) analogue, has any effect on the production of endogenous prostaglandins in iridial melanocytes, which could be important in the mechanism leading to increased pigmentation. Bovine and human iridial melanocytes in culture were used for the experiments. Production of endogenous prostaglandins was measured by enzyme immunoassay, and the melanin content was measured spectrophotometrically. In bovine iridial melanocytes, latanoprost acid caused a significant increase of the PGE(2) production, which could be blocked by indomethacin and NS398, indicating an involvement of cyclo-oxygenase 2. In order to study the selectivity of the phenomenon other endogenous substances/drugs were tested, e.g., acetylcholine, carbachol, noradrenaline, neuropeptide Y, substance P and alpha-MSH, but none was found to have any significant effect. Human iridial melanocytes also responded to latanoprost acid with increased production of PGE(2) and in 1 out of 5 individuals increased melanogenesis coincided with increased PGE(2) production. In bovine iridial melanocytes, latanoprost acid did not stimulate melanogenesis. These results indicate that latanoprost acid cause enhanced formation of endogenous prostaglandins that may have auto- and/or paracrine effects in the melanocytes, possibly associated with melanogenesis.
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PMID:Production of prostaglandin e(2) by iridial melanocytes exposed to latanoprost acid, a prostaglandin F(2 alpha) analogue. 1241 90

Glutamate exerts its effects through binding and activation of two classes of specific receptors: ionotropic (iGluRs) and metabotropic (mGluRs). Group I mGluR includes mGluR1 and mGluR5 subtypes, group II includes mGluR2 and mGluR3 subtypes and group III includes the subtypes mGluR 4, 6, 7 and 8. Glutamate and its receptors are found in all key hypothalamic areas critically involved in reproduction and neuroendocrine function. To date, considerable data support an important role for iGluRs in the control of neuroendocrine function; however, the role of mGluRs as regulators of hypothalamic-pituitary function has not been clearly elucidated. mGluRs could be exerting a fine tune on the release of hypothalamic factors that regulate hormone release such as Substance P, GABA, alpha-MSH and CRH. Group II mGluR exert a direct inhibitory effect on anterior pituitary prolactin and GH secretion. Moreover, some group II mGluR agonists, like LY 354,740 and LY 379,268, can modulate PRL secretion from the anterior pituitary through their actions as dopamine receptor agonists. Evidence suggests a role for group III mGluR subtypes in stress-related behavioral disorders. Several reports indicate that selective ligands for mGluR subtypes have potential for the treatment of a wide variety of neurological and psychiatric disorders, including depression, anxiety disorders, schizophrenia, epilepsy and Alzheimer's disease among others. Since converging lines of evidence suggest a role for mGluRs subtypes in neuroendocrine regulation of hormone secretion, mGluRs neuroendocrine actions must be taken in consideration to insure proper treatment of these diseases. Moreover, discovery of selective agonists provides an opportunity to investigate the physiological role of mGluR subtypes and to directly test the neuroendocrine actions of mGluRs. Finally, mGluRs selective agonists may have an impact in the treatment of conditions involving chronic stress, such as depression and anxiety disorders, since they regulate neuroendocrine stress circuits involving the HPA axis and stress-sensitive hormones such as oxytocin and prolactin. This review aims to provide a survey of our current understanding of the effects of mGluR activation on neuroendocrine function.
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PMID:Role of metabotropic glutamate receptors in the control of neuroendocrine function. 1861 55


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