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)

Previous studies have demonstrated that substance P- (SP) and calcitonin gene-related peptide-like immunoreactivities (CGRP-LI) coexist in sensory nerve fibres in the guinea-pig carotid body and carotid sinus. In the present study the ultrastructure of these nerve fibres was investigated by means of single- and double-labelling immunocytochemistry. In both, carotid body and carotid sinus immunoreactive fibres were unmyelinated axons of small diameter (0.12-0.56 microns). At the subcellular level, SP- and CGRP-LI were colocalized in intra-axonal dense core vesicles, suggesting corelease and simultaneous action of these two compounds. SP/CGRP-LI nerve fibres within the carotid body were mainly found in the interparenchymal connective tissue, but also occurred in relationship to blood vessels and nests of glomus cells. Neither in the carotid body not in the carotid sinus, SP/CGRP-LI axons corresponded to the large terminals which are generally considered to represent the main chemoreceptor and baroreceptor endings, respectively. Thus, SP/CGRP-LI fibres either belong to the chemo- and baroreceptors of the C-fibre class or constitute a fibre population not directly involved in conduction of baro- and chemoreflexes.
 ...
PMID:Ultrastructure of calcitonin gene-related peptide- and substance P-like immunoreactive nerve fibres in the carotid body and carotid sinus of the guinea pig. 247 19

This study uses radiological and immunocytochemical techniques to investigate the localization, content, transport and release of substance P- and calcitonin gene-related peptide-like immunoreactivity (SP-LI and CGRP-LI, respectively) in nerve fibre endings in 1-, 3- and 5-week-old cutaneous nerve neuromas. Neuromas were induced by ligating and transecting the saphenous nerve in anaesthetized Sprague-Dawley rats. The content of both neuropeptides in 3-week-old saphenous nerve neuroma was significantly reduced compared to that in normal saphenous nerve. At 5 weeks the levels of the peptides in the neuromas had returned to normal but remained reduced in the nerve just proximal to the neuroma. Following a 24-h ligation of the nerve proximal to 3-week-old neuromas there was a diminished immunocytochemical staining for SP-LI and CGRP-LI both proximal and distal to the ligature when compared to that seen at ligations of normal nerves. This indicates a decreased transport of the neuropeptides both to and from the 3-week-old neuromas. The density of neuropeptide staining at ligatures of nerves with 5 week or older neuromas had increased, but still remained less than that seen at ligations of normal nerve. Both a basal and a bradykinin-induced release of SP-LI and CGRP-LI from nerve fibre endings in the neuroma was demonstrated. The basal release was demonstrated by exposing the neuromas, in situ, to solutions containing 50 microM morphine plus 2 mM CoCl2 for 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The localization and release of substance P and calcitonin gene-related peptide at nerve fibre endings in rat cutaneous nerve neuroma. 248 63

The noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle was examined. Catecholamine-containing nerves were identified histochemically by glyoxylic acid-induced fluorescence and tyrosine hydroxylase immunoreactivity (TH-IR). The extrinsic pudic-epigastric artery and vein as well as the entire intramuscular arteriolar network was innervated by noradrenergic axons. The capillaries and intramuscular venules of the cremaster muscle were devoid of a noradrenergic innervation. Immunohistochemical double-labeling demonstrated that most, if not all, of the TH-IR axons also possessed neuropeptide Y immunoreactivity (NPY-IR), implying colocalization of the norepinephrine and NPY in the perivascular nerves. No vasoactive intestinal peptide immunoreactivity (VIP-IR) was found, except for occasional VIP-IR axons associated with the pudic-epigastric artery. Substance P immunoreactive (SP-IR) axons formed a sparse plexus around the arteries and larger arterioles. Calcitonin gene-related peptide immunoreactivity (CGRP-IR) had a similar distribution to the SP-IR axons. CGRP-IR was also observed in axons alongside some smaller arterioles and capillaries. The extrinsic vessels and intramuscular arteriolar network of the rat cremaster muscle are innervated by noradrenergic axons which contain NPY and by presumed sensory nerves containing SP and/or CGRP. Both types of nerves may contribute to regulation of microvascular function.
 ...
PMID:Noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle. 248 4

Peptide-containing nerves have been examined in the rat femoral artery and vein using immunocytochemical and vasomotor techniques. The general neuronal marker PGP 9.5 revealed a moderate supply of nerve fibres and fascicles forming a loose network in the adventitia and the adventitial-medial border of the artery and vein. The majority of the nerve fibres in both the artery and vein displayed immunoreactivity for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). The distribution pattern and number of these two types correlated well. The artery had a slightly richer PGP 9.5- immunoreactive nerve supply compared to the vein, but the nerve plexus in the vein displayed a more uniform arrangement. In contrast, relatively few nerve fibres displayed calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide immunoreactivity in either the artery or vein. The calcitonin gene-related peptide immunoreactive fibres had a similar distribution to that of the substance P containing fibres. Using a sensitive in vitro method the vasomotor responses to perivascular peptides were characterized. In the femoral artery NPY potentiated alpha 1-adrenoceptor mediated contractions, and had very little effect by itself. In contrast, 10(-7) M NPY contracted femoral veins by up to 68% relative to 60 mM potassium induced contraction, and there was no potentiation of alpha-adrenoceptor mediated contractions. Acetylcholine, peptide histidine isoleucine, vasoactive intestinal peptide, substance P and calcitonin gene-related peptide, all relaxed the contracted femoral artery and vein. Regarding the putative parasympathetic neurotransmitters, acetylcholine caused stronger relaxation of veins as compared to arteries whereas for vasoactive intestinal peptide and peptide histidine isoleucine the relaxations were stronger in the arterial preparation. These three agonists were more potent in the femoral vein. Substance P was more potent on the femoral vein, having the same maximum response in both preparations. On the other hand, the response induced by CGRP was some three times greater in the venous than in the arterial preparation. These data reveal that although there appear to be only minor differences in the peptidergic innervation of the rat femoral artery and vein pronounced differences occur in the peptide effector responses. The data support the concept that perivascular peptides play different roles in regulating various parts of the circulation.
 ...
PMID:Peptide-containing nerves in the rat femoral artery and vein. An immunocytochemical and vasomotor study. 248 49

By immunocytochemistry a number of the gut/brain peptides have been demonstrated in nerve fibers of the mammalian urogenital tract. These peptides are localized to large vesicles in nerve terminals of afferent fibers or efferent nerves innervating blood vessels, non-vascular smooth muscle, lining epithelium and glands. There is evidence that some neuropeptides (VIP, NPY) participate in the local non-cholinergic, non-adrenergic nervous control of smooth muscle activity and blood flow, while other peptides (substance P, CGRP) seem to be sensory transmitters. It is likely that impaired function of the peptidergic nerves is involved in sexual dysfunction such as male impotence.
 ...
PMID:Regulatory peptides in the mammalian urogenital system. 252 94

High-affinity binding sites for endothelin have been found in a human placenta membrane preparation. 125I-endothelin bound to placenta membranes at 20 degrees C with an association half-time of 30 min, whereas the binding was only slowly reversed with a dissociation half-time of 250 min. In saturation experiments, a single class of high-affinity binding sites was identified with an apparent dissociation constant (KD) of 24 pM and a maximal density of 240 fmol per mg of protein. The binding of 125I-endothelin was half-maximally inhibited by cold endothelin at a concentration (IC50) of 140 pM. In contrast, no inhibition was found at 10(-4) M for a variety of vasoactive peptides such as angiotensin II, vasopressin, neuropeptide Y, substance P, CGRP, bradykinin, leucine enkephalin or dynorphin A. Similarly, the binding was modulated neither by the calcium channel blockers nifedipine, verapamil or diltiazem, nor by the calcium channel agonist Bay k 8644. There was also no effect with the structurally-related bee venom apamin. Using this membrane preparation, endothelin-like activity could be measured in the medium of cultured human endothelial cells by competition binding technique.
 ...
PMID:Specific receptors for endothelin on membranes from human placenta. Characterization and use in a binding assay. 254 8

(1) We have studied the ability of some regulatory peptides to induce a mitogenic (incorporation of tritiated thymidine) response in human peripheral blood mononuclear cells (PBMC) and to modify the response produced by phytohaemagglutinin (PHA), a well known PBMC mitogen. (2) Human calcitonin gene-related peptide (hCGRP), human or salmon calcitonin (hCT, sCT), neurokinin A (NKA) and neurokinin (4-10) (up to 1 microM for each peptide) did not produce per se any significant PBMC stimulation. (3) hCGRP (0.1 nM-1 microM) produced a concentration dependent enhancement of the response to a submaximal concentration of PHA (1 microgram/ml). On the other hand, hCGRP decreased the mitogenic response to a maximal concentration of PHA (25 micrograms/ml). (4) Neither hCT nor sCT (0.1 nM-1 microM) had a significant influence on the response to PHA (1-25 micrograms/ml). (5) Both NKA and NKA (4-10) produced a concentration-dependent (1 fM-10 pM) enhancement of the response to 1 microgram/ml PHA, while these compounds had no effect on the response to 25 micrograms/ml PHA. (6) These findings suggest a potent modulatory action of CGRP and NKA, two peptides present in sensory and other nerves, on immune function which is possibly mediated via C2 receptors for CGRP and NK-2 tachykinin receptors, respectively.
 ...
PMID:Effects of calcitonin gene-related peptide (CGRP), neurokinin A and neurokinin A (4-10) on the mitogenic response of human peripheral blood mononuclear cells. 254 11

The immediate response of the rabbit eye to noxious stimulation is mediated neurogenically through antidromic sensory activation and subsequent action of neuropeptides, CGRP, and substance P or a related tachykinin. The rise in ocular tension and breakdown in the BAB in response to injury are initiated by dilation and increased permeability of the ciliary vessels, which bring about disruptive alterations in the squamous epithelium covering the anterior part of the iridial processes and ciliary ridge. PGs formed during the response to certain types of irritation can enhance the ocular changes to trauma by facilitating the neurogenic pathway. In the rabbit eye substance P acts as a strong miotic in response to injury but has no effect on the IOP rise or disruption of the BAB. Conversely, CGRP is a potent vasodilator that displays no spasmogenic action. Species differences in the ocular response to injury have been observed, with lower mammals such as rabbit and rat generally being more responsive than higher mammals. For the most part, these differences are related to the organization of the iris-ciliary complex and to the sensitivity of the effector elements to the neuromediators. Reciprocal modulation exists between the autonomic and sensory nervous elements and the tissue they innervate, so that altered sensitivity of the effector cells develops in selectively denervated eyes. Chronic sympathetic denervation causes hypersensitivity of the eye to irritation. This increase is owing largely to hypertrophied sensory elements with increased sensory neuropeptide levels and consequently augmented sensory activity. Conversely, chronic sensory denervation is accompanied by an increase in catecholamine-forming enzymes and in the neuropeptide NPY. Future research will no doubt reveal neuromodulation of homeostatic, inflammatory, and vegetative processes and the ability of ocular tissues to recover from wounding. Both the discovery of biogenic neuropeptides in peripheral nervous elements of the eye alongside the classical transmitters and the elucidation of their profound effects on the eye afford scope for the development of potential new therapeutic agents.
 ...
PMID:Mediation of the ocular response to injury and irritation: peptides versus prostaglandins. 267 45

Sympathetic and parasympathetic influences on the airway resistance under physiological and pathophysiological conditions have long been known. In recent years, this classical view had to be extended due to mounting evidence of neurocrine and paracrine peptide mediators. The term non-adrenergic non-cholinergic (NANC) nervous system was coined. Besides other effects the non-adrenergic mediators (e.g. VIP and PHI/PHM) give rise to bronchodilation, while the non-cholinergic modulators (SP, neurokinin A, and CGRP) induce bronchospasm. The axon-reflex theory postulates liberation of non-cholinergic peptide substances by afferent C-fibers exposed by bronchial epithelial cell damage as one important cause of bronchial obstruction. In addition to biogenic amines, such peptides as bombesin, leu-encephalin, beta-endorphin, calcitonin, doctrine cells of the bronchial epithelium. Our knowledge of the biological relevance of these mediators is at present very sketchy. Platelet activating factor (PAF) is released by alveolar macrophages, granulocytes, blood vessel endothelium, and platelets. The inhalation of PAF induces bronchospasm in healthy subjects and asthmatics and also prolonged bronchial hyperreactivity. The many factors influencing bronchial reactivity need to be classified by further investigations of the mode of interaction and interdependence of known and new mediators.
 ...
PMID:[The significance of endocrine, neurocrine and paracrine mediators in the regulation of bronchial reactivity]. 268 1

Human fetal spinal cord tissue was recovered from elective abortions and grafted to the anterior chamber of the eye of adult athymic nude rats. The transplants slowly became vascularized from the host iris during the first months. There was a clear cut stage-dependent survival and growth along a more "human" time-table. Fetal spinal cord tissue from embryos younger than gestational week 8 showed a much better survival and growth than tissue from older stages. Using laminin immunohistochemistry blood vessels could be visualized in the grafts. The pattern of vascularization was, however, clearly abnormal; there were fewer vessels which had abnormally thick walls as compared to those in the normal spinal cord. Similar to rat spinal cord allografts the human spinal cord xenografts displayed a relative gliosis and were surrounded by a glial layer visualized with antibodies against glial fibrillary acidic protein. Neurofilament-immunoreactive fibres were found inside the glial layer. A variety of neurons were found including large polygonal motoneuron-shaped cells, albeit with CGRP and AChE negative cell bodies. Both Substance P and enkephalin-immunoreactive cells and fibres were found. It is concluded that xenografted fetal human spinal cord survives, grows and may provide a useful model for experimental studies of human spinal cord development and connectivity.
 ...
PMID:Human fetal spinal cord xenografts survive in the eye of athymic nude rat hosts. 272 11


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