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)

We have prepared a series of conformationally constrained hexapeptide analogs of substance P which are 500-1500-fold more potent as inhibitors of 125I-labeled Bolton Hunter-conjugated eledoisin binding to rat brain cortex membranes than as inhibitors of 125I-labeled Bolton Hunter-conjugated substance P binding. These analogs stimulate guinea pig ileum contraction (ED50 1-16 nM) and stimulate rat vas deferens contraction (ED50 2-4 microM). However, these peptides are poor stimulators of rat salivation (greater than 40 nmol/100 g body weight). Thus, based on both their receptor potency and pharmacological potency, these peptides are potent and selective tachykinin analogs. These data indicate that a specific carboxyl-terminal conformation is recognized by the 125I-labeled Bolton Hunter-conjugated eledoisin binding site and that this conformation is different from the conformation recognized by the 125I-labeled Bolton Hunter-conjugated substance P binding site. Hexapeptides containing phenylalanine, isoleucine, and valine identical with the carboxyl-terminal sequences of substance P, eledoisin, and neurokinin B, respectively, were nearly equipotent as inhibitors of 125I-labeled Bolton Hunter-conjugated eledoisin binding. The valine analog was only approximately 5-fold less potent than the isoleucine and phenylalanine analogs as an inhibitor of 125I-labeled Bolton Hunter-conjugated substance P binding. Thus, unknown determinants in the amino-terminal sequences of substance P must strongly contribute to the carboxyl-terminal peptide selectivity and conformation. The contraction of guinea pig ileum induced by one of the conformationally constrained analogs is attenuated by pretreatment of the tissue with atropine (2 microM), while that induced by substance P methyl ester, a selective inhibitor of 125I-labeled Bolton Hunter-conjugated substance P binding, is not. Thus, the constrained analog has a higher affinity for the tachykinin receptors in the guinea pig myenteric plexus which are responsible for acetylcholine release than for the tachykinin receptors present on the smooth muscle cells.
 ...
PMID:Conformationally constrained tachykinin analogs which are selective ligands for the eledoisin binding site. 241 47

The respiratory tract has a rich supply of autonomic nerves. Among the neurotransmitter candidates are noradrenaline, neuropeptide Y, substance P, calcitonin-gene-related peptide, gastrin-releasing peptide, acetylcholine, vasoactive intestinal polypeptide, and peptide histidine isoleucine. The fibers are distributed around blood vessels and seromucous glands, and beneath and/or within surface epithelium. The distribution suggests that the fibers may influence blood flow, glandular secretion, and epithelial functions.
 ...
PMID:Innervation of the upper airways. 242 64

The gastrointestinal and respiratory tracts contain numerous regulatory peptides produced by and released from specialised epithelial cells and the organ innervation. This complex system of endocrine cells and nerves is generally called "the diffuse neuroendocrine system". Markers are now available which permit the visualisation of the diffuse neuroendocrine system or its individual components. These include antibodies to neuron-specific enolase, chromogranin, neurofilament triplet proteins, the brain protein S100 and antibodies to a variety of regulatory peptides. Peptides present in the gut and lung innervation include: vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), galanin, substance P, calcitonin gene-related peptide (CGRP), neuropeptide tyrosine (NPY), somatostatin and cholecystokinin (the latter two are also localised to endocrine cells of the gut). Bombesin-immunoreactivity is found in nerves in the gut and in endocrine cells of the foetal/neonatal lung. Neuropeptides of the gut and lung originate either from local neurons (e.g. VIP, PHI, galanin) or extrinsic neurons localised in sensory ganglia (e.g. substance P and CGRP) or the sympathetic chain (e.g. NPY). Recent studies point to the involvement of regulatory peptides in diseases of the gut and lung. These, together with detailed distribution studies, provide supportive data on the putative role of the peptides in the control of normal bowel and respiratory functions. The gastrointestinal and respiratory tracts were within the systems investigated by Feyrter during his original observations on the existence of specialised epithelial cells with a putative regulatory function (Feyrter, 1938). These "endocrine/paracrine" cells were found to be scattered in epithelial organs throughout the body. In fact, endocrine cells of the respiratory tract are frequently referred to as "Feyrter's cells". The term "regulatory peptides" was introduced as a generic term (Polak and Bloom, 1983) after the finding that active peptides are produced both by cells of the diffuse endocrine or APUD (amine precursor uptake and decarboxylation) system (Pearse, 1983) and autonomic/sensory nerves. These peptides are released into the circulation from endocrine cells or locally from nerve terminals or paracrine cells. The concept of "gut/brain" peptides was dispelled after the findings that the respiratory tract was provided abundantly with numerous active peptides produced by and released from mucosal endocrine cells and/or the innervation.
 ...
PMID:Regulatory peptides of the gastrointestinal and respiratory tracts. 242 59

The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose-dependent, long-lasting hyperpolarization of the Schwann-cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann-cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]-enkephalin) blocked the actions of all the above peptides as well as the effects of DL-octopamine and carbachol. The actions of [Met]-enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann-cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL-octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann-cell membrane. Evidence is presented for the existence of an endogenous VIP-like component in the normal hyperpolarizing action of giant-axon activity on the membrane potential of the Schwann cell.
 ...
PMID:Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre. 243 97

The effect of parasympathetic nerve activation on rabbit submandibular gland (SMG) blood flow and saliva secretion were studied before and after systemic administration of atropine or hexamethonium. The parasympathetic fibers were stimulated electrically (2 and 15 Hz, 10 V, 1 msec) at the plexus around the submandibular salivary duct or at the chorda lingual nerve. In untreated animals, stimulation of parasympathetic fibers caused a frequency-dependent increase of salivary secretion and blood flow in the SMG. Atropine treatment completely abolished saliva secretion at 2 Hz and 15 Hz and the increase in SMG blood flow during stimulation at 2 Hz. Although atropine significantly reduced the vasodilatory response at 15 Hz, the highest blood flow measured under such circumstances was still about 2.5 times the prestimulation value. After hexamethonium administration no blood flow increase or saliva secretion was seen upon chorda lingual stimulation. The concentration of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the venous effluent of the SMG increased during nerve stimulation. Atropine significantly reduced, and hexamethonium abolished this VIP-output elicited by parasympathetic nerve stimulation. Local infusion of VIP, peptide histidine isoleucine (PHI) and substance P all caused atropine-resistant vasodilation but no salivation. The present data suggest that VIP and possibly PHI play a role in the atropine-resistant vasodilatation in rabbit submandibular gland elicited by parasympathetic nerve stimulation. The contribution of sensory mediators such as substance P released by stimulation of afferent nerves in the chorda lingual nerve to the salivary and vasodilatory responses seems to be of minor importance in the rabbit submandibular gland.
 ...
PMID:VIP and noncholinergic vasodilatation in rabbit submandibular gland. 243 46

Neurons containing enkephalin, substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), galanin, calcitonin gene-related peptide (CGRP), peptide histidine isoleucine (PHI) or gastrin-releasing peptide (GRP) are known to occur in the human intestinal tract. The knowledge of the ontogeny of these neurones is, however, limited. Intestinal specimens from 24 human foetuses with gestational ages varying between 8 and 40 weeks were examined by immunocytochemistry. No peptide-containing neurones could be detected before the 14th week of gestation after which a rapid development was seen. Generally, peptide immunoreactivity was first noted in the myenteric ganglia and somewhat later in the other layers of the intestinal wall. There was no major difference between the peptides studied or between different parts of the intestinal tract with respect to time of appearance.
 ...
PMID:Ontogeny of peptide-containing neurons in human gut--an immunocytochemical study. 244 78

Nerve fibers containing neuropeptide Y, vasoactive intestinal polypeptide/peptide histidine isoleucine, substance P/neurokinin A (NKA), calcitonin-gene-related peptide (CGRP), and galanin are numerous in the respiratory tract. The fibers derive from several different ganglia such as the superior cervical and stellate ganglia, the jugular-nodose ganglionic complex, small ganglia along the vagus nerve, local ganglionic formations in the tracheal wall, and dorsal root ganglia at the cervical and thoracic level. The fibers surround vascular and nonvascular smooth muscle and seromucous glands and can be seen beneath the surface epithelium. In addition, nerve fibers containing substance P/NKA and CGRP penetrate into the surface epithelium. In some instances, neuropeptides are colocalized with "classic" neurotransmitters such as norepinephrine and acetylcholine; in other cases, several peptides coexist. Many of the neuropeptides affect blood flow, smooth muscle tone, and/or seromucous secretion. Some of them may take part in reflex-mediated responses. However, the lack of specific antagonists makes it difficult to define their functional role in the respiratory tract.
 ...
PMID:Neuropeptides in the airways: a review. 244 38

The distribution of peptide-immunoreactive neurons in the human retina was investigated. Neurons displaying immunoreactivity towards substance P, vasoactive intestinal polypeptide (VIP), somatostatin, neuropeptide Y (NPY) and peptide histidine-isoleucine (PHI) were found in amacrine cells with cell bodies situated in the innermost part of the inner nuclear layer and nerve fibers ramifying in the inner plexiform layer in a manner differing according to the peptide investigated. Two other cell types were found. In the middle of the inner plexiform layer cell bodies showing immunoreactivity towards substance P, VIP and PHI were found. In the ganglion cell layer there were cell bodies showing immunoreactivity towards substance P, somatostatin, VIP and NPY. Substance P immunoreactive, somatostatin and NPY immunoreactive fibers situated at the border between the inner nuclear and outer plexiform layers and traversing the inner nuclear layer were also found.
 ...
PMID:Peptide immunoreactive neurons in the human retina. 245 1

Levels of substance P (sP), peptide-histidine-isoleucine (PHI), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurotensin (NT), bombesin (BOM) and methionine-enkephalin (Met-Enk) like immunoreactivity were measured in cat, dog, primate and sloth cervical, thoracic, lumbar and sacral dorsal and ventral horns and dorsal root ganglia. The levels of peptides in the cat sacral cord and the principal peaks of immunoreactivity on a 10-60% acetonitrile gradient on a C18 reverse phase high performance liquid chromatography (HPLC) were sP (sP1-11: 369 ng/g), PHI (PHI: 271 ng/g), VIP (VIP1-28: 210 ng/g), Met-Enk (Met1-5 and extended forms: 257 ng/g), BOM (BOM1-10 and GRP1-27: 20 ng/g), CCK (CCK-8: 15 ng/g) and NT (NT1-13: 10 ng/g). Consideration of the rostrocaudal levels revealed an approximately even distribution with the exception of VIP and PHI which showed sacral/cervical ratios of 79 and 63. For sP, Met-Enk and BOM dorsal/ventral ratios were greater than 1 at all spinal levels. For VIP, PHI and CCK these ratios were greater than 1 only in the sacral cord. Dorsal root ganglion (DRG) levels of sP, VIP, PHI were readily measurable in single ganglia and covaried with the respective levels in the dorsal cord. Pooled samples of spinal ganglia and the trigeminal ganglia revealed that the relative levels of peptide immunoreactivity were: sP (25 ng/g); VIP (26 ng/g); PHI (28 ng/g); Met-Enk (6 ng/g); CCK (2 ng/g); NT (1 ng/g); and BOM (1 ng/g).
 ...
PMID:Survey of distribution of substance P, vasoactive intestinal polypeptide, cholecystokinin, neurotensin, Met-enkephalin, bombesin and PHI in the spinal cord of cat, dog, sloth and monkey. 245 58

By the use of light microscopic (LM) immunohistochemistry, the presence of peptides and of dopamine beta-hydroxylase (DBH) in nerves supplying mammalian (guinea pig, rat, cat, pig, mouse, human) lymph nodes were examined. In all species, lymph nodes of various somatic and visceral regions were found to contain nerve fibers which stained for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), calcitonin gene-related peptide (CGRP) or DBH. SP- and CGRP-immunoreactive (ir) fibers completely overlapped and exhibited the widest distribution. They were present in perivascular, paravascular and many non-vascular fibers travelling in close contact with lymphoid cells. In contrast, NPY-ir fibers coincided with those staining for DBH, prevailed in perivascular plexus and only rarely branched off into lymphoid parenchyma. Alternate staining of adjacent sections revealed that SP/CGRP-ir fibers were different from NPY/DBH-ir fibers. The distribution of VIP-ir fibers was identical to that of PHI-ir fibers and partially overlapped with that of ir-NPY/DBH or ir-SP/CGRP fibers. We conclude that the NPY innervation of lymph nodes is sympathetic noradrenergic while nerves coding for co-existing SP and CGRP are most likely of sensory origin. The nerves containing co-existing VIP and PHI may be of heterogenous origin (sensory, cholinergic sympathetic, and/or parasympathetic). We suggest that these distinct sensory and autonomic peptidergic pathways linking the nervous system with the lymph nodes may play a differential role in bidirectional neuroimmunomodulation.
 ...
PMID:Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation? 245 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>