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)

The native tachykinins cod neurokinin A and cod substance P, serotonin and acetylcholine have excitatory effects on the circular smooth muscle of the cod intestine. Furthermore, immunoreactivities to the cod tachykinins, serotonin and two markers for cholinergic neurones, viz. choline acetyltransferase and vesicular acetylcholine transporter, have been demonstrated in myenteric neurones of the cod intestine. In order to elucidate whether the neurones containing these substances project orally and thus might be involved in the ascending excitatory reflex of peristalsis, myotomy operations have been performed on the cod intestine. The immunoreactive areas of the myenteric plexus immediately oral and anal to the myotomy operations have been measured by using confocal laser scanning microscopy. Large accumulations of immunoreactivity to the tachykinins are found on the anal side of the myotomies, indicating oral projections of tachykininergic neurones. The areas immunoreactive to serotonin and choline acetyltransferase are of equal size on the oral and anal sides. Since the tachykinin containing neurones of the intestine project orally, and since cod neurokinin A and cod substance P have excitatory effects on circular smooth muscle, we conclude that tachykininergic neurones are involved in the ascending excitatory reflex of peristalsis in the cod intestine.
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PMID:Projections and actions of tachykininergic, cholinergic, and serotonergic neurones in the intestine of the atlantic cod. 947 97

Antibodies against choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) were used to determine whether neurons that have previously been identified as intrinsic primary afferent neurons in the guinea-pig small intestine have a cholinergic phenotype. Cell bodies of primary afferent neurons in the myenteric plexus were identified by their calbindin immunoreactivity and those in the submucous plexus by immunoreactivity for substance P. High proportions of both were immunoreactive for ChAT, viz. 98% of myenteric calbindin neurons and 99% of submucosal substance P neurons. ChAT immunoreactivity also occurred in all nerve cell bodies immunoreactive for calretinin and substance P in the myenteric plexus, but in only 16% of nerve cells immunoreactive for nitric oxide synthase. VAChT immunoreactivity was in the majority of calbindin-immunoreactive varicosities in the myenteric ganglia, submucous ganglia and mucosa and also in the majority of the varicosities of neurons that were immunoreactive for calretinin and somatostatin and that had been previously established as being cholinergic. We conclude that the intrinsic primary afferent neurons are cholinergic and that they may release transmitter from their sensory endings in the mucosa.
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PMID:Immunohistochemical localisation of cholinergic markers in putative intrinsic primary afferent neurons of the guinea-pig small intestine. 972 54

The occurrence and colocalization of several biologically active neuropeptides, catecholamine-, acetylcholine- or nitric oxide-synthesizing enzymes-tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H), choline acetyl-transferase (ChAT) and nitric oxide synthase (NOS I), respectively, as well as the vesicular acetylcholine transporter (VAChT) were investigated in the penile glans (GP), corpus and crura (CP), as well as in the retractor penis muscle (RPM) of juvenile and adult boars. Immunohistochemistry revealed that nerves immunoreactive (IR) to TH, D beta H, vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) were the most numerous, followed (in decreasing order of density) by nerves IR to NOS, neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), galanin (GAL), Leu5-enkephalin (LENK) and ChAT/VAChT. The CP contained the largest number of nerve fibres followed by the RPM, GP and corpus. Enzyme/peptide-containing nerves were associated with both the vascular and non-vascular penile structures. However, differences existed for their density and intrapenile distribution. Nerve terminals IR for different combinations of VIP, GAL or SOM were more frequent than those IR for NOS or CGRP in the non-vascular penile structures while the vasculature and the RPM received a prominent TH/D beta H-, VIP-, SOM- or NOS-IR nerve input. The present data indicate that the porcine penis receives nerve fibres that exhibit diverse chemical codes and that differences in the chemical coding of the nerve fibres may depend on their penile target-structure.
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PMID:Innervation of the fibro-elastic type of the penis: an immunohistochemical study in the male pig. 1009 43

The synaptic relationship between substance P (SP) and its receptor, i.e., neurokinin-1 receptor (NK1R), was examined in the striatum of the rat by confocal laser-scanning microscopy and electron microscopy. For confocal laser-scanning microscopy, triple-immunofluorescence histochemistry was performed to label NK1R, SP, and vesicular acetylcholine transporter (a specific marker for cholinergic neurons). In electron microscopic double-immunolabeling study, immunoreactivity for NK1R was detected with the silver-intensified gold method, while immunoreactivity for SP was detected with peroxidase immunohistochemistry. Simultaneous immunolabeling of NK1R and SP revealed significant mismatch at the synaptic level: although some SP-immunopositive axon terminals were in synaptic contact with NK1R-immunopositive sites of plasma membrane, NK1R-immunoreactivity was observed at both synaptic and non-synaptic sites of plasma membrane. Thus, SP released from the sites remote from NK1Rs might diffuse in the extracellular fluid to act, as a paracrine neurotransmitter, on NK1Rs distant from its releasing site. SP neurotransmission in the striatum might occur not only synaptically but also extrasynaptically. The SP-NK1R system might constitute an association system within the striatum.
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PMID:Relationship between neurokinin-1 receptor and substance P in the striatum: light and electron microscopic immunohistochemical study in the rat. 1070 41

Double-label in situ hybridization was used to identify the phenotypes of striatal neurons that express mRNA for cannabinoid CB(1) receptors. Simultaneous detection of multiple mRNAs was performed by combining a (35)S-labeled ribonucleotide probe for CB(1) mRNA with digoxigenin-labeled riboprobes for striatal projection neurons (preprotachykinin A, prodynorphin, and preproenkephalin mRNAs) and interneurons (vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT), somatostatin, and glutamic acid decarboxylase (Mr 67,000; GAD67) mRNAs). To ascertain whether CB(1) mRNA was a marker for striatal efferents, digoxigenin-labeled probes for mRNA markers of both striatonigral (prodynorphin or preprotachykinin A mRNAs), and striatopallidal (proenkephalin mRNAs) projection neurons were combined with the (35)S-labeled probe for CB(1). A mediolateral gradient in CB(1) mRNA expression was observed at rostral and mid-striatal levels; in the same coronal sections the number of silver grains per cell ranged from below the threshold of detectability at the medial and ventral poles to saturation at the dorsolateral boundary bordered by the corpus callosum. At the caudal level examined, CB(1) mRNA was denser in the ventral sector relative to the dorsal sector. Virtually all neurons expressing mRNA markers for striatal projection neurons colocalized CB(1) mRNA. Combining a (35)S-labeled riboprobe for CB(1) with digoxigenin-labeled riboprobes for both preproenkephalin and prodynorphin confirmed localization of CB(1) mRNA to striatonigral and striatopallidal neurons expressing prodynorphin and preproenkephalin mRNAs, respectively. However, CB(1) mRNA-positive cells that failed to coexpress the other markers were also apparent. CB(1) mRNA was localized to putative GABAergic interneurons that express high levels of GAD67 mRNA. These interneurons enable functional interactions between the direct and indirect striatal output pathways. By contrast, aspiny interneurons that express preprosomatostatin mRNA and cholinergic interneurons that coexpress ChAT and VAChT mRNAs were CB(1) mRNA-negative. The present data provide direct evidence that cannabinoid receptors are synthesized in striatonigral neurons that contain dynorphin and substance P and striatopallidal neurons that contain enkephalin. By contrast, local circuit neurons in striatum that contain somatostatin or acetylcholine do not synthesize cannabinoid receptors. Published 2000 Wiley-Liss, Inc.
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PMID:Localization of cannabinoid CB(1) receptor mRNA in neuronal subpopulations of rat striatum: a double-label in situ hybridization study. 1084 53

Substance P (SP) is the major endogenous ligand for neurokinin 1 (NK1) receptors and, together with acetylcholine, has an important role in motivated behaviors involving the limbic shell and motor core of the nucleus accumbens (NAc). To determine the functional sites for SP activation of NK-1 receptors and potential interactions with cholinergic neurons in these regions, the authors examined the electron microscopic immunocytochemical localization either of antisera against the NK1 receptor or of the NK1 receptor and either 1) SP or 2) the vesicular acetylcholine transporter (VAchT) in rat NAc. In both the NAc shell and core, NK1 receptor labeling was localized mainly to somatic and dendritic plasma membranes and nearby endosomal organelles in aspiny neurons. In sections through the ventromedial shell that were processed for NK1/SP labeling, 46% of the NK1-immunoreactive dendrites (n = 603 dendrites) showed symmetric or appositional contacts with SP-containing terminals. These terminals and several others that formed symmetric synapses also occasionally were immunoreactive for NK1 receptors. Analysis of the shell region for NK1/VAchT labeling showed that 61% of the total immunoreactive dendrites (n = 534 dendrites) contained NK1 receptors without VAchT, 29% contained both products, and 10% contained VAchT only. Many of the labeled somata and dendrites also received synaptic contact from VAchT-containing terminals. These findings suggest that, in the NAc, NK1 receptors are recycled through endosomal compartments and play a role in modulating mainly the postsynaptic responses, but also the presynaptic release, of SP and/or inhibitory neurotransmitters onto aspiny interneurons, some of which are cholinergic.
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PMID:Neurokinin 1 receptor distribution in cholinergic neurons and targets of substance P terminals in the rat nucleus accumbens. 1087 89

The myenteric plexus of the gastrointestinal tract was investigated in the obese diabetic mouse, an animal model of human type 2 diabetes. Sections were immunostained by the avidin-biotin complex method, using a general nerve marker, protein gene product 9.5 (PGP 9.5), as well as antibodies to several important neurotransmitters. Computerized image analysis was used for quantification. When diabetic mice were compared with controls, no difference was found in the density of PGP 9.5-immunoreactive (IR) nerve fibres in antrum, duodenum or colon. In antrum and duodenum, diabetic mice showed a decreased number of vasoactive intestinal peptide (VIP)-IR neurons in myenteric ganglia as well a decreased relative volume density in myenteric plexus (though not significantly in antrum, p=0.073). No difference was found regarding VIP-IR nerves in colon. The volume density of nitric oxide synthase (NOS)-IR nerve fibres was decreased in antrum and duodenum of diabetic mice, whereas no difference was found in colon. The density of galanin-IR nerve fibres was decreased in duodenum. Whereas neuropeptide Y (NPY)- and vesicular acetylcholine transporter (VAChT)-IR nerve fibres was increased in density in colon of diabetic mice, no difference was found in antrum and duodenum. Regarding substance P, there was no difference between diabetic and control mice in antrum, duodenum or colon. The present study shows that gut innervation is affected in this animal model of human type 2 diabetes. It is possible that the present findings may have some relevance for the gastrointestinal dysfunctions seen in patients with type 2 diabetes.
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PMID:Myenteric plexus of obese diabetic mice (an animal model of human type 2 diabetes). 1119 91

Ganglion cells and topographically related nerves in the vallate papilla/von Ebner gland complex were investigated in rat tongue by cytochemical, immunocytochemical, and ultrastructural methods to evaluate the possible presence of different neuronal subpopulations. Immunostaining for neurofilaments and protein gene product 9.5 revealed ganglionic cell bodies and nerve fibers. A large part of the neurons were positive at immunostaining for neuronal nitric oxide synthase (NOS), vesicular acetylcholine transporter (VAChT), or vasoactive intestinal peptide (VIP). A small subset of nerve fibers revealed immunoreactivity for cholecystokinin. Axons traveling under the lingual epithelium were evidenced by their content of calcitonin gene-related peptide (CGRP) or substance P (SP). Cell bodies positive for SP or CGRP were not detected. Using methods of co-localization, three different neuronal classes were detected. The main population was composed of AChE/NADPH-diaphorase (NADPHd)-positive cells. Small groups of acetylcholine esterase (AChE)-positive/NADPHd-negative cells were visible. Isolated neurons were AChE-negative/NADPHd-positive. The results of co-localization experiments for VAChT/NOS were consistent with those obtained by cytochemical co-localization of AChE and NADPHd. Experiments of co-localization for peptidergic and nitrergic structures revealed CGRP- and SP-immunoreactive fibers in the vallate papilla/von Ebner gland ganglion. In conclusion, the results demonstrated in the VP/VEG complex peptidergic, cholinergic, and nitrergic neurons. The presence of different neuronal subclasses suggests that a certain degree of functional specialization may exist.
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PMID:Ganglion cells and topographically related nerves in the vallate papilla/von Ebner gland complex. 1196 82

Despite the known major role of skin blood vessel innervation in blood flow control, particularly in disease, little information on the co-innervation of blood vessels by sensory and autonomic fibers and the relationships of these fibers to one another is available. To fill this gap, we performed a light and electron microscopic analysis of the innervation of skin vessels by sensory and autonomic fibers by using the rat and monkey lower lips as a model. In rats, double-labeling immunocytochemistry revealed that combinations of fibers immunoreactive for substance P (SP) and dopamine-beta-hydroxylase (DbetaH), SP and vesicular acetylcholine transporter (VAChT), as well as DbetaH and VAChT occurred only around blood vessels in the lower dermis. All fiber types travelled in parallel and in close proximity to one another. In the upper dermis, blood vessels were innervated by SP-containing fibers only. Although nerve terminals displayed synaptic vesicles, synaptic specializations were never observed, suggesting that, in this territory, these fibers do not establish synaptic contacts. Quantification of the distance between the various immunoreactive terminals and their presumptive targets (smooth muscle cells and endothelial cells) revealed that both sympathetic and parasympathetic fibers were significantly closer to the endothelial cell layer and smooth muscle cells compared with sensory fibers. In monkeys, double-labeling immunocytochemistry was performed for SP-DbetaH and SP-VAChT only. The results obtained are similar to those found in rats; however, the fiber density was greater in monkeys. Our findings suggest that the regulation of skin microcirculation might be the result of the coordinated functions of sensory and autonomic fibers.
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PMID:Skin blood vessels are simultaneously innervated by sensory, sympathetic, and parasympathetic fibers. 1211 96

Nerve fibres play an important role in the regulation of gastric emptying. The aims of this study were to clarify the distribution, projections and origin of neuronal type nitric oxide synthase (NOS)-, tyrosine hydroxylase (TH)-, vesicular acetylcholine transporter (VAchT)- and peptide-containing nerve fibres of the rat pyloric sphincter. Extrinsic and local denervations of the sphincter were performed in order to reveal the origin and projections of the various nerve fibre populations. Pylorus from control and denervated animals were processed for the immunocytochemical demonstration of cholecystokinin (CCK), enkephalin, gastrin-releasing peptide (GRP), somatostatin, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating peptide (PACAP), substance P (SP), vasoactive intestinal peptide (VIP), galanin, NOS, VAchT and TH. VAchT, TH, nNOS, and all of the peptides investigated were found in nerve fibres innervating the pyloric sphincter, and coexistence of several putative neurotransmitters were revealed. Extrinsic denervation caused a total loss of NPY/TH-, SP/CGRP- and SP/CGRP/VIP/NOS/PACAP-containing nerve fibres. Local denervation immediately proximal to the sphincter markedly reduced the numbers of VIP/NOS/galanin- and VIP/NOS/galanin/PACAP +/- NPY-containing fibres within the sphincter suggesting an origin of these fibres in myenteric ganglia in the antral region; denervation at the level of the oxyntic-pyloric border had no effect. Local denervation immediately distal to the sphincter caused a marked decrease in VAchT-, SP/enkephalin-, enkephalin-, somatostatin-, CCK- and GRP-containing fibres within the sphincter suggesting that these emanate from the duodenum. The latter procedure also reduced the number of SP/CGRP-containing fibres of extrinsic origin within the pyloric sphincter.
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PMID:Origins and projections of nerve fibres in rat pyloric sphincter. 1213 47


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