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 dopamine (DA)-sensitive adenylate cyclase in the substantia nigra was assayed in rats which had been subjected to 3 different kinds of brain lesion: (1) unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle; (2) unilateral lesions of the descending strio-nigral and pallido-nigral projections; (3) total lesions of the serotoninergic raphe-nigral pathway. Lesions of the medial forebrain bundle causing 97% depletion of striatal DA, 72% depletion of nigral tyrosine hydroxylase, and no change in nigral glutamate decarboxylase (GAD), resulted in no change in basal or DA-stimulated cyclic AMP production ipsilateral to the injection. Lesions of the globus pallidus, causing 70% and 79% reductions in GAD and substance P respectively in the ipsilateral nigra, produced a reduction in basal cyclic AMP production and abolished the normal increase in cyclic AMP produced by DA on the side of the lesion. Lesions to the dorsal and median raphe nuclei did not affect the normal DA-sensitive adenylate cyclase response in the nigra. The results suggest that one of the neurotransmitter functions of DA in this brain region may be to modulate the release of psi-aminobutyric acid (GABA) or substance P from synaptic terminals afferent to the nigra.
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PMID:Evidence concerning the anatomical location of the dopamine stimulated adenylate cyclase in the substantia nigra. 2 89

Morphological and pharmacological data suggest that catecholaminergic neurons receive afferent axons positively labeled for the peptides, substance P and [Met5]-enkephalin. In the present study, electron microscopic immunocytochemistry was used to determine whether a positive reaction for these peptides could be localized to axon terminals forming synapses with catecholaminergic neurons in the locus coeruleus and A2 regions of rat brain. Adjacent sections through these areas were incubated with antiserum to either substance P, [Met5]-enkephalin, or tyrosine hydroxylase, a specific marker for catecholaminergic neurons. The sections were subsequently processes by the peroxidase-antiperoxidase immunocytochemical technique. In both the locus coeruleus and A2 region, tyrosine hydroxylase was localized primarily to perikarya and dendrites of intrinsic neurons; whereas substance P and enkephalin-like immunoreactivity was localized to axons and axon terminals. The axon terminals showing positive reactions for substance P and [Met5]-enkephalin were morphologically similar to each other and to one type of axon terminal which formed synapses with dendrites labeled for tyrosine hydroxylase. This type of axon terminal always formed asymmetric synaptic junctions and contained 3-4 large (75-100 nm) dense vesicles (LDVs) and many small (40-60 nm) clear vesicles (SCVs). The reaction product for substance P and [Met5]-enkephalin was distributed throughout the lumen of the LDVs and formed a rim of labeling around the outer boundaries of the SCVs. These findings demonstrate that substance P and [Met5]-enkephalin-positive reactions are selectively localized to subcellular organelles in axon terminals in the locus coeruleus and A2 region of rat brain. They further suggest that the labeled axon terminals form synapses with dendrites of the catecholaminergic neurons.
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PMID:Electron microscopic localization of substance P and enkephalin in axon terminals related to dendrites of catecholaminergic neurons. 3 43

Neuronal antigens can be demonstrated histologically by numerous direct and indirect immunocytochemical techniques in which a specific antibody is identified by a marker compound such as fluorescein isothiocyanate, ferritin, or horseradish peroxidase. One of the more sensitive methods for the light and electron microscopic localizations of antigens in sections of tissue is the peroxidase-antiperoxidase (PAP) technique. The experimental procedures and the results obtained using this technique for the localization of the catecholamine synthesizing enzyme, tyrosine hydroxylase, are described. The cellular and ultrastructural localization of the enzyme is demonstrated in perikarya, processes, and terminals of catecholaminergic neurons in rat brain. The immunocytochemical localization of tyrosine hydroxylase is compared to the localization of two peptides, substance P and [Met5]-enkephalin, in the A2 region of the medulla. These studies suggest that a synaptic interaction exists between the catecholaminergic neurons and neurons showing positive immunoreactivity for the peptides. The limitations of the PAP immunocytochemical technique are also discussed in relation to the immunocytochemical localization of tyrosine hydroxylase and other antigens.
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PMID:Immunocytochemical localization of neuronal antigens: tyrosine hydroxylase, substance P, [Met5]-enkephalin. 3 6

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.
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PMID:Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. 127 91

We previously showed that long-term hypoxia increases the dopamine content in rat laryngeal nerve paraganglia. In the present study paraganglia of rats exposed to hypoxia (10 +/- 0.5% O2) for 14 days were examined immunohistochemically to detect changes in the expression of neuropeptides and catecholamine-synthesizing enzymes. Hypoxia induced an intense cellular substance P (SP)-like immunoreactivity (LI) in some paraganglia and an increase in the number of stromal nerve fibers showing SP-LI in others. The patterns of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, phenylethanolamine-N-methyltransferase-, vasoactive intestinal polypeptide-, neuropeptide-Y and calcitonin gene-related peptide-LI were not changed in response to hypoxia. The results show that hypoxia induces changes in the pattern of SP immunoreactivity in laryngeal nerve paraganglia and may indicate that SP plays a role in the regulation of catecholamine metabolism in this tissue.
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PMID:Long-term hypoxia induces changes in the substance P immunoreactivity pattern in laryngeal nerve paraganglia. 127 34

Deer antler is a unique mineralized tissue which can produce very high growth rates of > 1 cm/day in large species. On completion of antler growth, the dermal tissues which cover the antler are shed and the underlying calcified tissue dies. After several months the old antler is discarded and growth of a new one begins. It is known that deer antlers are sensitive to touch and are innervated. The major aims of this study were to identify and localize by immunohistochemical techniques the type of innervation present, and to find out whether nerve fibres could exhibit growth rates comparable to those of antler. We have taken tissue sections from the tip and shaft of growing Red deer (Cervus elaphus) antlers at three stages of development; shortly after the initiation of regrowth, the rapid growth phase, and near the end of growth. Incubation of tissue sections with antisera to protein gene product 9.5 (a neural cytoplasmic protein), neurofilament triplet proteins (a neural cytoskeletal protein), substance P and calcitonin gene-related peptide (both of which are present in and synthesized by sensory neurons) showed the presence of immunoreactive nerve fibres in dermal, deep connective and perichondrial/periosteal tissues at all stages of antler growth. The sparse distribution of vasoactive intestinal polypeptide-like immunoreactivity was found in dermal tissue only at the earliest stage of antler development. Nerve fibres immunoreactive to neuropeptide Y, C-flanking peptide of neuropeptide Y and tyrosine hydroxylase, all present in postganglionic sympathetic nerves, were not observed at any stage of antler growth. Nerves expressing immunoreactivity for any of the neural markers or peptides employed could not be found in cartilage, osteoid or bone. These results show that antlers are innervated mainly by sensory nerves and that nerves can attain the exceptionally high growth rates found in regenerating antler.
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PMID:Rapid neural growth: calcitonin gene-related peptide and substance P-containing nerves attain exceptional growth rates in regenerating deer antler. 128 Mar 52

In order to study the relationship between retinal projections and immunohistochemically identified neurotransmitter systems in the primary visual centers of the brain in lizards, intraocular injections of horseradish peroxidase were combined with immunohistochemistry. Antibodies raised against six substances were applied: choline acetyltransferase (ChAT), serotonin (5-HT), tyrosine hydroxylase (TH), dopamine (DA), substance P (SP), and leu-enkephalin (LENK). In the primary visual centers of the lizards Gekko gecko and Gallotia galloti, notable overlap was observed between retinofugal fibers with: 1) ChAT-immunoreactive fibers in almost all primary visual centers; 2) 5-HT-immunoreactive fibers in the ventral lateral geniculate body and the basal optic nucleus; 3) TH-immunoreactive fibers in the nucleus ovalis and the dorsal lateral geniculate body; 4) SP- and LENK-immunoreactive fibers in the perirotundal belt; and 5) TH- and SP-immunoreactive fibers in the pretectal posterodorsal nucleus. The latter nucleus also contains dopaminergic cell bodies that lie outside the retinal target area but have dendrites extending into it. Several differences were noted in the distribution of 5-HT, TH-, DA-, and LENK-immunoreactive fibers in the tectum of the midbrain in the two species studied. Distinct laminae of 5-HT-immunoreactive fibers (layer 9) and TH- and DA-immunoreactive fibers (layers 9 and 11) are present in G. gecko but absent or, at least, less distinct in G. galloti. On the contrary, the optic layers in the tectum of G. galloti show a rather dense plexus of LENK immunoreactive fibers, whereas the corresponding layers in G. gecko are devoid of LENK-immunoreactivity. Since only a very few ChAT immunoreactive fibers were observed in the optic nerve of G. galloti, most of the observed immunoreactive fibers in the primary visual centers are considered to have an extraretinal origin. Putative sources of the cholinergic, the monoaminergic, and the peptidergic innervation of the primary visual centers in reptiles include the isthmic nucleus, the raphe nuclei, the substantia nigra and the nucleus of the posterior commissure, as reported in other amniotes.
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PMID:Cholinergic, monoaminergic and peptidergic innervation of the primary visual centers in the brain of the lizards Gekko gecko and Gallotia galloti. 128 May 14

A peroxidase anti-peroxidase method or an avidin-biotinylated complex method was used to visualize neural elements immunostained for several neuropeptides in the chicken pancreas. Pancreatic ganglion cells were only immunoreactive with vasoactive intestinal polypeptide (VIP), galanin and substance P (SP) antisera. VIP-immunoreactive (IR) ganglion cells were the most numerous, and most of them also showed the distinct immunoreaction with galanin. VIP- and galanin-IR nerve fibers were observed in the exocrine portion, the adventitia of the artery and the connective tissue of the ductal wall. The number and distribution of the VIP- and galanin-IR nerve fibers around the artery and duct were similar. SP-IR nerve fibers were found mainly close to the blood vessel. SP- and CGRP-IR nerve fibers were detected in the VIP-IR ganglion and extrapancreatic nerve bundle. Tyrosine hydroxylase (TH)- and aromatic L-amino acid decarboxylase (AADC)-IR nerve fibers were observed as nerve bundles in the interlobular space or extrapancreatic nerves. Consequently, VIP and galanin coexist in the intrinsic neural elements. SP is partially located in the intrinsic neural elements, but most of it seems likely to originate from the extrinsic ganglion. It is probable that calcitonin gene related peptide (CGRP)-, TH- and AADC-IR nerve fibers have an extrinsic origin.
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PMID:Immunohistochemical studies on the intrinsic pancreatic nerves in the chicken. 128 86

We have used immunofluorescence to study the postnatal development of the sympathetic and sensory innervation to the rhesus monkey (Macaca mulatta) ovary. Sympathetic nerves were identified as adrenergic by their content of tyrosine hydroxylase (TH)-like immunoreactivity and as peptidergic by the presence of neuropeptide Y (NPY). Fibers containing substance P (SP) or calcitonin gene-related peptide (CGRP)-like immunoreactivity were considered as sensory, whereas vasoactive intestinal peptide (VIP)-positive fibers were only defined as peptidergic because VIP may be present in both sympathetic and sensory nerves. Ovaries from neonatal (2-mo-old), juvenile (9-18-mo-old), peripubertal (3-3.5-yr-old), adult (9-14-yr-old), and senescent (20-27-yr-old) monkeys were studied. At all ages, with the exception of senescence, TH-, NPY-, and VIP-containing fibers were associated with follicles in different developmental stages. In peripubertal and adult animals, some primordial follicles were found to be selectively innervated by VIPergic fibers that almost completely encircled each follicle. Both sympathetic and VIP fibers were also detected in the interstitial tissue and associated with the ovarian vasculature at all ages. The number of sympathetic and VIP fibers increased significantly (p < 0.01) between 2 mo and 9-18 mo of age, and again increased (p < 0.01) around the age of puberty (approximately 3 yr of age). After this time, the number of NPY and TH fibers remained constant. Conversely, the number of VIP fibers decreased (p < 0.05) by 9-14 yr of age, but remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postnatal development of sympathetic and sensory innervation of the rhesus monkey ovary. 128 72

Hypoxic stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15-20 microns) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20-29 microns) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic "efferent" inhibition in the carotid body.
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PMID:Transmitter diversity in carotid body afferent neurons: dopaminergic and peptidergic phenotypes. 128 13


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