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)

Kinins are endogenously formed peptides that have diverse biological actions, including effects on the gastrointestinal tract. In the search of selective ligands, we studied the binding properties of a selective B2 radioiodinated antagonist (Tyr,D-Arg[Hyp3,D-Phe7,Leu8]BK) on epithelial membranes of guinea pig ileum. Equilibrium binding experiments showed that 125I-Tyr,D-Arg[Hyp3,D-Phe7,Leu8]BK specifically labels two different sites. One of these sites is the conventional B2 receptor. The new tracer recognized this site with a Kd of 34.7 nM and revealed a Bmax of 156 fmol/mg protein. In equilibrium binding experiments 125I-Tyr,D-Arg[Hyp3,D-Phe7,Leu8]BK also recognized a second specific site. Scatchard analysis showed that this second site was of high affinity (Kd of 16.8 nM) and very abundant (Bmax of 2.08 pmol/mg protein). Surprisingly, the natural B2 agonists bradykinin and kallidin were unable to inhibit the specific binding of 125I-Tyr,D-Arg[Hyp3,D-Phe7,Leu8]BK to the second site. A series of B2 antagonists failed to inhibit the specific binding of the new radiolabelled peptide. As expected, non related peptides such as angiotensin II, neurokinin A and B, substance P, vasopressin, calcitonin gene related peptide and bombesin were also inactive. These results show that the new tracer is interacting with two distinct binding sites in epithelial membranes of guinea pig ileum. One is the well known bradykinin B2 receptor and the other is a new, non characterized binding site that interacts exclusively with bradykinin receptor antagonists.
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PMID:125I-Tyr,D-Arg[Hyp3,D-Phe7,Leu8]BK, a radiolabelled B2 antagonist specifically interacts with two distinct binding sites on epithelial membranes of guinea pig ileum. 133 30

Immunocytochemistry and a radioimmunoassay were used to investigate the existence and distributions of various regulatory peptide immunoreactivities (ir) in human submandibular and parotid glands. Numerous nerve fibers containing vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), or neuropeptide tyrosine (NPY) and C-flanking peptide of NPY (CPON)-ir were found in close proximity to acini, ducts and blood vessels. Only a few calcitonin gene-related peptide (CGRP)- and substance P (SP)-ir nerve fibers could be demonstrated and were mainly localized around blood vessels and ducts. Galanin and the recently discovered peptides helospectin and pituitary adenylate cyclase activating peptide were unable to be detected in the salivary glands studied. Preliminary quantitative investigations of four human submandibular glands using radioimmunoassay showed that VIP-ir had the highest concentration, followed by NPY-ir and CGRP-ir; SP-concentrations were below the detection limit. The possible physiological significance of these peptides for salivary secretion is discussed.
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PMID:[Peptidergic innervation of human salivary glands (parotid gland and submandibular gland)]. 133 45

We evaluated the effect of intrathecal (i.t.) capsaicin (CAP) and the NK-1 selective non-peptidic antagonist, CP,96-345, on the thermal hyperalgesia ordinarily observed after unilateral partial ligation of the sciatic nerve in rats. CAP was injected i.t. 2 days after constriction injury. Seven days after partial ligation, the levels of substance P (sP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were the same in the left and right dorsal horns of the lesioned rats which were injected with vehicle (VEH). CAP (75 micrograms/15 microliters of 20% 2-hydroxypropyl-beta-cyclodextrin) resulted in an equal reduction (40-50%) in the dorsal horn levels of sP and CGRP, but not VIP. After 7 days, i.t. CAP increased the paw withdrawal latency (PWL) of the non-injured hind paw. In contrast, there was no change in the PWL of the injured paw when compared to that of VEH-treated animals. Thus, CAP did not abolish the hyperalgesic state. We concluded that the thermal hyperalgesia after sciatic nerve constriction injury is not mediated by CAP-sensitive C fibers. CP,96-345 given i.t. at a dose which is physiologically active (400 micrograms) had little effect on the thermal response latency of either the normal or hyperesthetic paw. This provides further evidence that neither the normal pain response nor hyperalgesic state is dependent upon a dorsal horn action of sP.
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PMID:Effects of intrathecal capsaicin and an NK-1 antagonist, CP,96-345, on the thermal hyperalgesia observed following unilateral constriction of the sciatic nerve in the rat. 133 98

A syngeneic transplantation of 150 islets into the subcapsular renal space was performed on normoglycemic or alloxan-induced diabetic male C57BL/6 mice. Six, 8, 14, or 20-21 wk after transplantation, the graft-bearing kidney was removed and processed for microscopical examinations with indirect immunofluorescence for neuropeptides and tyrosine hydroxylase, and with acetylcholinesterase staining to visualize nerve fibers within the graft. Six weeks after implantation, only a few scattered nerve fibers were observed within the grafts. A progressive increase in the number of nerves was observed until 14 wk after transplantation, after which, a stable level was reached. Alloxan-induced diabetic mice showed quantitatively and qualitatively similar reinnervation to normoglycemic mice 20 wk after transplantation. The findings demonstrate the presence of sympathetic nerve fibers (containing tyrosine hydroxylase and neuropeptide Y), mainly accompanying ingrowing blood vessels; parasympathetic nerve fibers (containing acetylcholinesterase and vasoactive intestinal peptide), possibly reaching the graft from the adjacent renal capsule; and afferent nerve fibers (containing substance P and calcitonin gene-related peptide), which were less numerous. The data suggest that transplanted islets become reinnervated by ingrowth of nerve fibers from the implantation organ and that several types of nerves are present.
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PMID:Reinnervation of syngeneic mouse pancreatic islets transplanted into renal subcapsular space. 134 84

We have demonstrated that the mouse neuroblastoma N18Tg2 cell line and several clones of hybrid ND cells (ND7, ND9 and ND21), derived from the fusion of neonatal rat sensory neurons with that neuroblastoma, show immunostaining to protein gene product 9.5, neuropeptide Y, C-flanking peptide of neuropeptide Y, tyrosine hydroxylase and chromogranins. Synaptophysin could only be detected in ND cells. Immunoreactivities to substance P, calcitonin gene-related peptide, galanin and somatostatin could not be detected in any of these cell lines. After three days of incubation in a differentiation medium, cell processes of various lengths were observed both in neuroblastoma and ND cell cultures. In ND7 cells there was also a redistribution of neuropeptide Y and its C-flanking peptide to the tips of cell processes. The differentiation of cell processes was also accompanied by the appearance of immunostaining to rat chromogranins in their tips. In contrast, synaptophysin expression was found mainly in cell bodies. Neuropeptide Y, its C-flanking peptide and chromogranins have been associated with secretory granules, whereas synaptophysin is a marker for small synaptic-like vesicles. Therefore, our morphological findings further support and expand the view that these markers are primarily associated with different subcellular structures. Moreover, they indicate that the regulated secretory pathway associated with chromogranins is segregated into nerve processes at an early stage of differentiation, when the synaptophysin-associated pathway is not yet mature. ND7 cells thus provide a useful model system for studying changes in the distribution of neuropeptides, cytoskeletal elements and proteins associated with cell secretion during neuronal differentiation.
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PMID:Intracellular redistribution of neuropeptides and secretory proteins during differentiation of neuronal cell lines. 134 12

Electrical field stimulation of circular muscle strips from the guinea-pig isolated renal pelvis produces a frequency-dependent positive inotropic effect of the spontaneous contractions which is unaffected by atropine and guanethidine and abolished by tetrodotoxin or in vitro capsaicin desensitization. Omega conotoxin fraction GVIA markedly inhibited the response to low frequencies of stimulation but had only a partial or minor inhibitory effect at higher frequencies. Tachykinins produce a concentration-dependent positive inotropic effect, neurokinin A being more potent than substance P. On the other hand, rat alpha calcitonin gene-related peptide (CGRP) inhibited spontaneous contractions of the renal pelvis. MEN 10,376 a neurokinin A (4-10) analog, antagonized the positive inotropism produced by neurokinin A, without affecting the response to KCl, and suppressed the positive inotropic response produced by electrical field stimulation. In the presence of MEN 10,376, a negative inotropic response was produced by electrical field stimulation which was antagonized by the C-terminal fragment (8-37) of human alpha calcitonin gene-related peptide (hCGRP). hCGRP (8-37) antagonized the negative inotropic effect of exogenously administered CGRP without affecting inhibition by isoprenaline. Application of capsaicin (10 microM) produced a marked increase in the outflow of substance P-, neurokinin A- and CGRP-like immunoreactivities from the superfused guinea-pig renal pelvis. Substance P-, neurokinin A- and CGRP-like immunoreactivities were also detected in tissue extracts of the renal pelvis by radioimmunoassay. These experiments indicate that peptide release from peripheral endings of capsaicin-sensitive primary afferents represents the major type of nerve-mediated response affecting motility of the guinea-pig isolated renal pelvis. Tachykinins and CGRP act as physiological antagonists and the excitatory action of tachykinins prevails over the inhibitory action of CGRP. Local modulation of renal pelvis motility by sensory nerves could facilitate removal of irritants present in the urine, protecting the kidney during obstruction and ureteral antiperistalsis.
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PMID:Tachykinins and calcitonin gene-related peptide as co-transmitters in local motor responses produced by sensory nerve activation in the guinea-pig isolated renal pelvis. 134 51

1. The vasomotor responses to neuropeptides of the angular oculi and facial veins of reindeer were examined in vitro and correlated with the neuropeptide distribution in the perivascular nerves, as demonstrated by immunohistochemistry. 2. Nerves displaying calcitonin gene related peptide (CGRP)- or neuropeptide Y (NPY)-like immunoreactivity (-LI) were observed in the media of both veins, while very few fibers were immunoreactive to vasoactive intestinal polypeptide (VIP) or substance P (SP) in either vein. 3. The staining pattern for NPY-LI was largely identical to that of dopamine-beta-hydroxylase, a marker for noradrenaline (NA) producing fibers, indicating coexistence of NPY and NA. 4. Administration of NPY in vitro elicited contractions in both veins in the presence of propranolol, though more conspicuously in the angular oculi vein. 5. The peptide was without any modulating effect on NA-stimulated contractions in the angular oculi vein, whereas a small enhancement of the NA-induced tone was seen in the facial vein. 6. CGRP caused partial relaxation of both veins, whereas atrial natriuretic polypeptide caused relaxation only in the facial vein. VIP and SP had no effect on either vein. 7. The results suggest that in reindeer the sympathetic nerve fibres to both facial and angular oculi veins contain the vasoconstrictor neuropeptide NPY besides NA, even though these fibres exert a vasodilator action on the myogenically active facial vein. 8. The vasodilator neuropeptide CGRP, which is present in other more sparse perivascular nerve fibres mainly in angular oculi vein, is perhaps of afferent nature in which case CGRP might subserve axon reflex functions. 9. If, however, also the CGRP fibres are truly efferent in nature, chances for a central reciprocal control of flow through angular oculi vein might be at hand.
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PMID:Distribution and vasomotor effects of neuropeptides in angular oculi and facial veins of reindeer. 134 61

Several neurotransmitters have been reported to exist in the ganglionated plexus of the guinea pig gallbladder. These include substance P, neuropeptide Y (NPY), calcitonin gene-related peptide, vasoactive intestinal peptide (VIP), acetylcholine, norepinephrine, serotonin, and dopamine. To determine which neuropeptides are intrinsic to gallbladder ganglia, we performed immunohistochemistry on colchicine-treated preparations. In separate, single-labeled preparations, a majority of neurons contained substance P-, NPY-, or somatostatin-like immunoreactivity. In double-labeled preparations, a large majority of the neurons that contained substance P-like immunoreactivity also contained NPY-like immunoreactivity and somatostatin-like immunoreactivity. Immunoreactivity for VIP was present in a small percentage of the gallbladder neurons which did not contain substance P-like immunoreactivity. Additional experiments were done to test for the presence of other compounds, known to exist in the neurons of the gut. Although immunoreactivity was found in control preparations of small intestine, the ganglionated plexus of the gallbladder lacked immunoreactivity for galanin, dynorphin, enkephalin, gastrin-releasing peptide, or gamma-aminobutyric acid. We conclude that ganglia of the guinea pig gallbladder contain at least two populations of neurons, based on transmitter phenotype. One of these populations appears to contain substance P, NPY, and somatostatin. Another population, which represents a small contingent of the total population of neurons, contains VIP.
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PMID:Transmitter diversity in ganglion cells of the guinea pig gallbladder: an immunohistochemical study. 134 12

Previous retrograde tracing studies on rat and guinea-pig showed a projection of sensory tyrosine hydroxylase-immunoreactive neurons to the region of the carotid bifurcation via the carotid sinus nerve. In the present study, focussing on the sensory innervation of the human carotid body, antisera to tyrosine hydroxylase and other catecholamine synthesizing enzymes were applied for an immunohistochemical investigation of carotid bodies obtained at autopsy. In addition, an array of antisera directed to non-enzyme antigens known to be present in viscero-afferent neurons were incorporated in the study. The glomic lobules consisting of glomus cells and sustentacular cells contained a variable number of enzyme-immunoreactive glomus cells. Arteries were supplied by nerve fibres displaying the full phenotype of sympathetic noradrenergic axons, i.e. immunoreactivity to tyrosine hydroxylase, aromatic-L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. The glomic lobules, however, were densely innervated by tyrosine hydroxylase-immunoreactive axons lacking immunoreactivity to aromatic-L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. These fibres reacted with neurofilament 160kD-antibody but were devoid of immunoreactivity to all neuropeptides tested (calcitonin gene-related peptide, somatostatin, substance P). Ultrastructurally, tyrosine hydroxylase/neurofilament 160kD-immunoreactive axons gave rise to large axonal swellings filled with mitochondria and vesicles, and established extensive contacts to glomus cells. Nerve bundles surrounded by a perineural sheath contained both myelinated (2.0-2.8 microns in diameter) and unmyelinated (0.14-3.0 microns) tyrosine hydroxylase-immunoreactive axons. Most of the unmyelinated immunoreactive axons were running singularly within a Schwann cell-sheath. Judged from the pattern of immunoreactivities as well as their preterminal and terminal ultrastructure, tyrosine hydroxylase-immunoreactive axons innervating glomus cells are of sensory origin. Although final proof by retrograde tracing cannot be presented in man, this conclusion is supported by experimental evidence in laboratory animals. The myelinated immunoreactive axons correspond to chemoreceptor A-fibres whereas the classification of the large unmyelinated immunoreactive axons has yet to be established. The lack of immunoreactivity to the dopamine-synthesizing enzyme, aromatic-L-amino-acid-decarboxylase, in this fibre type does not support the view of dopamine being the primary transmitter of chemoreceptor afferents.
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PMID:Chemoreceptor A-fibres in the human carotid body contain tyrosine hydroxylase and neurofilament immunoreactivity. 135 71

Immunohistochemistry has been used to demonstrate that neuropeptide Y, dopamine-beta-hydroxylase, calcitonin gene-related peptide or substance P are colocalized with vasoactive intestinal polypeptide and choline acetyltransferase in subpopulations of neurons in cranial parasympathetic ganglia of rat. These comprise the ciliary, sphenopalatine, otic, glossopharyngeal-vagal and internal carotid ganglia. In the ciliary and glossopharyngeal-vagal ganglia tyrosine hydroxylase is also found in such neurons. The findings emphasize that the combined localization of dopamine-beta-hydroxylase and neuropeptide Y or the presence of tyrosine hydroxylase is not exclusively a marker for peripheral adrenergic neurons. Further, the co-localization of calcitonin gene-related peptide and substance P is not a decisive indication that a neuron is sensory in nature. It is discussed whether the presence of the enzymes and peptides other than vasoactive intestinal polypeptide is a remnant of a different expression during ontogenesis or indicates target-specific functions in the adult.
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PMID:Vasoactive intestinal polypeptide and acetylcholine coexist with neuropeptide Y, dopamine-beta-hydroxylase, tyrosine hydroxylase, substance P or calcitonin gene-related peptide in neuronal subpopulations in cranial parasympathetic ganglia of rat. 135 Sep 46


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