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 aim of the present in vitro study was to provide information on the pharmacologic properties of the muscularis mucosae in three regions of the rabbit colon. Proximal muscularis mucosae exhibited spontaneous contractions whose frequency was independent of endogenous acetylcholine. In the mid and distal colon, spontaneous contractile frequencies were depressed by atropine and enhanced by eserine. Muscularis mucosae from all regions responded to acetylcholine, ADP, AMP, ATP, bradykinin, histamine, methoxamine, substance P, vasoactive intestinal polypeptide but not cholecystokinin octapeptide or gamma-aminobutyric acid. Low concentrations of norepinephrine caused propranolol-sensitive relaxations of proximal colonic muscularis mucosae whereas high concentrations evoked phentolamine-sensitive contractions. In the mid and distal colon, norepinephrine caused relaxations which were poorly antagonized by propranolol. Proximal colonic muscularis mucosae responded to electrical stimulation with an atropine- and tetrodotoxin-sensitive "on contraction." Responses from the mid and distal colon were tetrodotoxin-sensitive and consisted of an atropine-sensitive "duration contraction" followed by a propranolol-insensitive "off relaxation" which was not mediated by prostaglandin synthesis, a purine, or vasoactive intestinal polypeptide. These data suggest that the rabbit colonic muscularis mucosae possesses alpha-1 adrenoceptors, histamine H1, muscarinic, P2 purinoceptors and beta adrenoceptors. However, their relative importance and the nature of the intrinsic innervation suggests considerable specialization of this muscle layer in different regions of the rabbit colon.
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PMID:Pharmacologic characterization of the muscularis mucosae in three regions of the rabbit colon. 160 78

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. We have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in two human inflammatory diseases, ulcerative colitis and Crohn's disease, using quantitative receptor autoradiography. The sensory neurotransmitter receptors included bombesin, calcitonin gene-related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only binding sites for substance P and vasoactive intestinal peptide were significantly altered in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.
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PMID:Alterations in receptors for sensory neuropeptides in human inflammatory bowel disease. 165 49

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Although it seems highly likely that mammalian isocortex evolved from a structure resembling reptilian telencephalic cortex, it has been uncertain if this occurred by the laminar differentiation of three-layered reptilian cortex into six-layered mammalian isocortex without the addition of new cell types or by laminar differentiation with the addition of new cell types. To distinguish between these two possibilities, immunohistochemical techniques were used to study turtles to see if the same major neuronal cell types, as defined by neurotransmitter or neuropeptide content, present in mammalian isocortex are also present in the specific part of reptilian cortex thought to be the forerunner of at least parts of isocortex, namely the dorsal cortex. Neurons containing the following substances are the major transmitter-specific types of neurons known to be present in mammalian isocortex: cholecystokinin-8 (CCK8), vasoactive intestinal polypeptide (VIP), acetylcholine, substance P (SP), neuropeptide Y (NPY), somatostatin (SS), LANT6, enkephalin, GABA and glutamate (GLUT). In turtles, only those of the above substances that are found in large numbers of neurons in layers V-VI in mammalian isocortex, irrespective of whether they are also present in layers II-IV (i.e. SP, NPY, SS, LANT6, GABA and GLUT), were present in neurons in dorsal cortex. The neurons containing these substances in dorsal cortex in turtles were generally highly similar in morphology to their counterparts in mammalian isocortex. In contrast, neurons labeled for CCK8, VIP or acetylcholine, which are mainly found in neurons of layers II-IV of mammalian isocortex, were absent or extremely rare in dorsal cortex. The absence or paucity of neurons labeled for these latter substances in dorsal cortex in turtles did not reflect an overall staining failure of the antisera used since the same antisera yielded excellent labeling of neurons, fibers and terminals in many other brain regions in turtles. Thus, dorsal cortex in turtles appears to lack several of the major cell types characteristic of layers II-IV of mammalian isocortex, but possesses a number of the major cell types characteristic of layers V-VI of isocortex. The findings support and extend a previous suggestion by Ebner [1976], based on hodological data, that dorsal cortex in turtles may lack the types of neurons found in the more superficial layers of mammalian isocortex.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A comparison of neurotransmitter-specific and neuropeptide-specific neuronal cell types present in the dorsal cortex in turtles with those present in the isocortex in mammals: implications for the evolution of isocortex. 168 5

Endocrine cells in the gastrointestinal tract of the domestic duck were identified immunocytochemically using antisera specific to bombesin, chromogranin A, cholecystokinin (CCK), gastrin, glucagon, neuron specific enolase (NSE), neurotensin, secretin, 5-hydroxytryptamine (5-HT), somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Chromogranin A, 5-HT and somatostatin immunoreactive cells were widespread throughout the gastrointestinal tract. Bombesin immunoreactive cells were observed only in the proventriculus and the gizzard. CCK, substance P and neurotensin immunoreactive cells were present in the intestinal tracts from the duodenum to the colorectum. The latter were numerous also in the antrum. Gastrin cells were peculiar to the antrum but present also in the gizzard and small intestine. Glucagon immunoreactive cells were present in the jejunum-ileum and above all in the large intestine. Only few secretin cells were present in the duodenum. The highest frequency of endocrine cells was found in the antrum, while the lowest was observed in the caeca. Antisera to somatostatin and substance P showed numerous nerve cells and fibers besides endocrine cells, whereas NSE and VIP immunopositivity was found in the nervous structures only of the gut wall.
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PMID:An immunohistochemical study on the endocrine cells in the gastrointestinal tract of domestic duck. 168 96

The lateral geniculate complex (GL) of pigeons was investigated with respect to its immunohistochemical characteristics, retinal afferents, and the putative transmitters/modulators of its neurons. The distributions of serotonin-, choline acetyltransferase-, glutamic acid decarboxylase-, tyrosine hydroxylase-, neuropeptide Y- (NPY), substance P- (SP), neurotensin- (NT), cholecystokinin- (CCK), and leucine-enkephalin- (L-ENK) like immunoreactive perikarya and fibers were mapped. Retinal projections were studied following injections of Rhodamine-B-isothiocyanate into the vitreous. Transmitter-specific projections onto the visual Wulst and the optic tectum were studied by simultaneous double-labelling of retrograde tracer molecules and immunocytochemical labelling. The GL can be divided into three major subdivisions, the n. geniculatus lateralis, pars dorsalis (GLd; previously designated as the n. opticus principalis thalami, OPT), the n. marginalis tractus optici (nMOT), and the n. geniculatus lateralis, pars ventralis (GLv). All three subdivisions are retinorecipient. The GLd can be further subdivided into at least five components differing in their immunohistochemical characteristics: n. lateralis anterior (LA); n. dorsolateralis anterior thalami, pars lateralis (DLL), n. dorsolateralis anterior thalami, pars magnocellularis (DLAmc); n. lateralis dorsalis nuclei optici principalis thalami (LdOPT); and n. suprarotundus (SpRt). The LdOPT consists of an area of dense CCK-like and NT-like terminals of probable retinal origin. Three subnuclei (DLL, DLAmc, SpRt) were shown to project to the visual Wulst. Cholinergic and cholecystokinergic relay neurons participated in this projection. The nMOT occupies a position between the GLd and GLv and encircles the rostral pole of n. rotundus and the LA. It is characterized mainly by medium sized NPY-like perikarya which were shown to project onto the ipsilateral optic tectum. Bands of NPY-like fibers in the tectal layers 2, 4, and 7 could at least in part be due to this projection of the nMOT. Most of the antisera used revealed transmitter/modulator-specific fiber systems in the GLv which often showed a layer-specific distribution. Perikaryal labelling was only obtained with glutamic acid decarboxylase. On the basis of its chemoarchitectonics, topography, and connectional pattern, the GLd complex of pigeons is most directly equivalent to the mammalian GLd. However, although the different subdivisions of the avian GLd may represent functionally different channels within the thalamofugal pathway similar to the lamina-specific differentiation within the mammalian geniculostriate projection, direct comparison of subnuclei of birds and mammals is not justified at this time. The nMOT appears similar to the intergeniculate leaflet (IGL) and the avian GLv clearly corresponds in many features to the mammalian GLv.
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PMID:An immunocytochemical analysis of the lateral geniculate complex in the pigeon (Columba livia). 168 43

First incubating guinea pig pancreatic acini with carbachol reduced the subsequent stimulation of amylase release caused by carbachol, cholecystokinin octapeptide (CCK-8), and bombesin but not that caused by vasoactive intestinal peptide, substance P, 8-bromoadenosine 3',5'-cyclic monophosphate, A23187, or 12-O-tetradecanoylphorbol-13-acetate. Carbachol also reduced the subsequent binding of N-[3H]methylscopolamine, 125I-CCK-8, and 125I-[Tyr4]bombesin. Pancreatic acini possess a high-affinity class of cholinergic receptors and a low-affinity cholinergic receptors appears to produce the reduction in carbachol-stimulated amylase release and binding of N-[3H]methylscopolamine. First incubating acini with carbachol caused a complete loss of high-affinity cholinergic receptors with no change in the number or affinity of low-affinity cholinergic receptors. Carbachol occupation of low-affinity cholinergic receptors appears to produce the reduction in CCK-8- and bombesin-stimulated amylase release and in binding of 125I-CCK-8 and 125I-[Tyr4]bombesin. Acini possess two classes of CCK receptors. One class has a high affinity for CCK-8; the other class has a low affinity for CCK-8. First incubating acini with carbachol caused a 60% decrease in the number of high-affinity CCK receptors with no change in the number of low-affinity receptors or the affinities of either class of receptors for CCK-8. Acini possess a single class of bombesin receptors, and first incubating acini with carbachol caused a 40% decrease in the number of bombesin receptors with no change in their affinity for bombesin. 12-O-tetradecanoyl phorbol-13-acetate reproduced the action of carbachol on binding of N-[3H]methylscopolamine and 125I-CCK-8 but not on binding of 125I-[Tyr4]bombesin, suggesting that carbachol activation of protein kinase C may in some way mediate the effect of carbachol on receptors for carbachol and those for CCK but not that on receptors for bombesin.
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PMID:Carbachol desensitizes pancreatic enzyme secretion by downregulation of receptors. 168 17

The occurrence and distribution of an array of neuropeptides and dopamine-beta-hydroxylase in the circumvallate papillae of monkey, pig, cow, ferret, cat, rat and mouse was studied by immunocytochemistry. The animals were chosen to represent species with different diets. Substance P/neurokinin A- and calcitonin gene-related peptide-containing fibers were numerous in the circumvallate papillae of all animals examined, with the highest frequency in monkey, pig, cow, rat and mouse; in ferret and cat moderate numbers were detected. Vasoactive intestinal peptide/peptide histidine isoleucine amide-containing fibers were numerous in the circumvallate papillae of pig, while they were moderate in number in monkey, ferret and mouse. Neuropeptide Y-containing fibers were few to moderate in number in the circumvallate papillae of all species. Galanin-containing fibers were numerous in the pig circumvallate papillae, while only a few fibers could be detected in monkey, cow, cat, rat and mouse. Somatostatin-containing fibers were seen only in the cat circumvallate papillae, gastrin-releasing peptide-containing fibers in the cow and cat, cholecystokinin/gastrin-containing fibers in the pig and cow. Dopamine-beta-hydroxylase-containing fibers were detected in all animals studied. They were few to moderate in number in the circumvallate papillae. There was no obvious link between the peptidergic innervation pattern and the food habits.
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PMID:Peptide-containing nerve fibers in the circumvallate papillae. 169 15

Adenosine receptors capable of modulating tachykininergic transmission were characterized in functional studies using both field-stimulated and cholecystokinin octapeptide-stimulated contractile responses of atropinized guinea pig longitudinal muscle-myenteric plexus preparations. These tetrodotoxin-sensitive responses, which were mediated by release of one or more tachykinins, were inhibited by adenosine analogs in a concentration-dependent manner. The rank order of potencies of the analogs as inhibitors of the responses to cholecystokinin octapeptide was N6-cyclopentyladenosine greater than 5'-N-ethylcarboxamidoadenosine much greater than 2-phenylaminoadenosine (CV 1808). Schild analysis of the antagonism of the presynaptic inhibitory effects of 5'-N-ethylcarbocamidoadenosine and N6-cyclopentyladenosine on cholecystokinin octapeptide-stimulated responses using the A1 selective antagonists 1,3-dipropyl-8-(4-sulfophenyl)xanthine and 1,3-dipropyl-8-(cyclopentyl)xanthine yielded linear isoboles with unit slopes indicating competitive antagonism. The affinity of the antagonists for the receptor site(s) involved in inhibition of tachykininergic transmission was similar to those established previously for cholinergic transmission. The rank order of potency of adenosine analogs as inhibitors of the field-stimulated responses was such that N6-cyclopentyladenosine = 5'-ethylcarboxamidoadenosine. Reverse-phase high-performance liquid chromatography analysis performed on lysates of isolated myenteric nerve endings demonstrated the presence of substance P and neurokinin-A. Neurokinin-B was undetectable. These studies indicate that adenosine receptor(s) on myenteric nerve endings are coupled negatively to tachykinin release and that they are probably identical to those involved in the modulation of acetylcholine release.
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PMID:Adenosine receptors are coupled negatively to release of tachykinin(s) from enteric nerve endings. 169 84

Immunocytochemical analysis of the thoraco-abdominal ganglia of the flies Drosophila melanogaster and Calliphora vomitoria revealed neurons displaying substance P- (SPLI), FMRFamide-(FLI), and cholecystokinin-like (CCKLI) immunoreactivity. It could be demonstrated that a number of neurons contain peptides reacting with antisera against all the three types of substances, others were either FLI or CCKLI alone. No neurons displayed only SPLI. Instead, the total number (about 30) of SPLI neurons constitute a subpopulation of the FLI/CCKLI neurons. Many of the identifiable immunoreactive neurons seem to be homologous in the two fly species. One set of six large neurons, termed ventral thoracic neurosecretory neurons (VTNCs), are among those that are SPLI, FLI, and CCKLI in both Drosophila and Calliphora. With the present immunocytochemical technique, the detailed morphology of the VTNCs could be resolved. These neurosecretory neurons supply the entire dorsal neural sheath of the thoraco-abdominal ganglia with terminals, thus forming an extensive neurohaemal area. The VTNCs also have processes connecting the thoracic neuromeres to the cephalic suboesophageal ganglion, as well as extensive arborizations in the thoracic ganglia, suggesting an important role in integrating and/or regulating large portions of the central nervous system, in addition to their neurosecretory function. Most of the other SPLI, FLI, and CCKLI neurons in the thoraco-abdominal ganglia seem to be interneurons. However, there are four FLI neurons that appear to be efferents innervating the hindgut and a few abdominal FLI and CCKLI neurons may be additional neurosecretory cells. From the present study it appears as if neuropeptides related to substance P, FMRFamide and CCK have roles as neurotransmitters/neuromodulators and circulating neurohormones in Drosophila and Calliphora.
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PMID:Substance P-, FMRFamide-, and gastrin/cholecystokinin-like immunoreactive neurons in the thoraco-abdominal ganglia of the flies Drosophila and Calliphora. 169 42


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