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)

1. Prostaglandin E (PGE) may be essential for maintaining the sensitivity of the myenteric plexus of guinea-pig ileum to nicotine. The contributions of prostaglandins to nervous activity evoked by different stimuli have now been investigated by measuring the amount of acetylcholine (ACh) released from the myenteric plexus of the guinea-pig ileum. 2. The amount of ACh released in response to dimethylphenylpiperazinium (DMPP) or substance P was depressed to about 40% of control by 2.8 microM indomethacin (Ind), whereas the release of ACh induced by 5-hydroxytryptamine (5-HT) was not affected. The inhibitory effects of Ind were overcome by 14.3 nM PGE2. 3. Mepacrine 5 microM, an inhibitor of phospholipase A2, depressed the release of ACh in response to DMPP and substance P to the same extent as Ind. These inhibitory effects of mepacrine were overcome by arachidonic acid (10 microM), but not by arachidonic acid plus Ind. The release of ACh evoked by 5-HT or electrical field stimulation (EFS) was also inhibited to about 60% of control by mepacrine but these inhibitions were overcome by arachidonic acid (10 microM) either in the absence or the presence of Ind. 4. The results suggest that endogenous prostaglandins and arachidonic acid contribute to the maintenance of the excitability of the myenteric plexus by DMPP and substance P. By contrast, the release of ACh induced by 5-HT and EFS may be regulated by arachidonic acid and not by prostaglandins.
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PMID:The differential contribution of endogenous prostaglandins to the release of acetylcholine from the myenteric plexus of the guinea-pig ileum. 170 12

This study examined whether dopamine (DA) is necessary for the normal development of striatal enkephalin and striatonigral tachykinin peptide systems. The neurotoxin, 6-hydroxydopamine (6-OHDA) was used to induce DA deficiency on the third day of the postnatal period in Sprague-Dawley rat pups. The animals were sacrificed at 60 days of age. The levels of Met5-enkephalin (ME) and substance P (SP) were determined by radioimmunoassay and preproenkephalin (PPE) and preprotachykinin (PPT) mRNA abundance in the striatum were assessed by hybridization analysis. The concentrations of DA, 5-hydroxytryptamine (5-HT) and their acid metabolites were determined by high-pressure liquid chromatography with electrochemical detection. The lesioned animals were grouped on the basis of the degree of loss of DA, and changes in ME, SP and 5-HT systems were correlated with respect to the degree of DA loss. The nature and extent of the changes in these systems were dependent on the degree of DA depletion. A loss of more than 90% DA was necessary to result in increased levels of ME and its PPE mRNA and reduced levels of SP and its PPT mRNAs; however, increased levels of 5-HT could be observed at a lower degree of DA loss. The results indicate that the normal development of enkephalin and tachykinin and 5-HT systems of basal ganglia are dependent on the availability of DA and/or the integrity of the nigrostriatal dopaminergic neurons. The results are relevant to our further understanding of the neurobiology of DA deficiency disorders.
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PMID:The adaptation of enkephalin, tachykinin and monoamine neurons of the basal ganglia following neonatal dopaminergic denervation is dependent on the extent of dopamine depletion. 170 18

Recently, two compounds have been developed, designated septide and senktide, which are highly selective agonists for the substance P receptor, types NK-1 and NK-3, respectively. Each of these, when injected intrathecally in awake rats, produced a distinct and non-overlapping constellation of sensory and behavioural effects which were subsets of the symptoms evoked by intrathecal administration of substance P. Prior systemic administration of 5-hydroxytryptamine (5-HT), alpha-adrenergic and opiate receptor antagonists, at doses sufficient to block the behavioural effects of the corresponding receptor agonists, did not alter responses to intrathecally injected septide or senktide. This was so, even for symptoms which suggested inhibitory mediation, hypoalgesia and (transient) motor flaccidity. Septide and senktide, administered by lumbar puncture and by indwelling catheter, produced identical results. Finally, in contrast to some other peptides, flaccid paralysis induced by senktide was not accompanied by spinal necrosis.
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PMID:Neurochemical mediators of the behavioural effects of receptor-selective substance P agonists administered intrathecally in the rat. 170 12

The ganglionated plexus of the guinea pig pancreas was investigated by using histochemical, immunocytochemical, and tract-tracing methods in order to determine whether pancreatic ganglia are analogous to the ganglia of the enteric nervous system (ENS). Three lines of evidence suggest that the ganglia of the pancreas appear to be interconnected with one another, as are enteric ganglia. First, microinjections of the retrograde tracer Fluoro-Gold into individual pancreatic ganglia labeled the perikarya of neurons in distant pancreatic ganglia, whereas no labeling of neurons was observed if injections were placed in the connective tissue adjacent to pancreatic ganglia. Second, when the intercalating dye DiI was microinjected into single pancreatic ganglia in fixed tissues, DiI-labeled terminals were found in additional pancreatic ganglia. Finally, microinjections of the beta subunit of cholera toxin into individual pancreatic ganglia yielded similar results. The ganglionated plexus of the pancreas also expresses a diversity of transmitter content and cell type-specific localization of monoamine oxidase (MAO) that is analogous to the ENS. In common with guinea pig enteric ganglia, pancreatic ganglia contain highly varicose 5-hydroxytryptamine (5-HT)-immunoreactive axons and intrinsic neuropeptide Y (NPY)- and substance P (SP)-immunoreactive neurons. The vast majority, but not all, of SP-immunoreactive fibers in the pancreatic parenchyma also contain calcitonin gene-related peptide (CGRP) immunoreactivity. MAO-B was the primary type of MAO found in the intrinsic elements of the pancreas where it was located in neurons and fibers in the pancreatic parenchyma. In common with serotoninergic enteric neurons, MAO-B immunoreactivity was not found at the LM level in pancreatic serotoninergic neurites. In contrast, NPY- and tyrosine hydroxylase (TH)-immunoreactive perivascular axons were found to contain abundant MAO-A, but no MAO-B immunoreactivity. It is concluded that MAO-B immunoreactivity is characteristic of a portion of the intrinsic innervation of the pancreas, whereas MAO-A immunoreactivity is a marker for the extrinsic sympathetic innervation of the pancreas. Because of its receipt of a direct neural innervation from myenteric ganglia of the bowel (Kirchgessner and Gershon, '90: J. Neurosci 10:1626-1642), similar connections, transmitter content and localization of type-specific MAO, the ganglionated plexus of the pancreas should be regarded as an extension or subset of the ENS.
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PMID:Guinea pig pancreatic ganglia: projections, transmitter content, and the type-specific localization of monoamine oxidase. 171 Jun 27

This study examined whether a relationship exists between the degree of dopamine (DA) loss and the changes in opioid (Met5-enkephalin, ME; dynorphin A (1-8) (DYN)) or tachykinin (substance P, SP) peptidergic systems in basal ganglia (caudate and putamen) and limbic (frontal cortex) regions of postmortem tissue samples derived from patients who died of Parkinson's disease (PD). The levels of ME, SP and DYN were determined by radioimmunoassays. The levels of DA and 5-hydroxytryptamine (5-HT) and their metabolites were determined by HPLC with electrochemical detection. The degree of loss of DA in PD tissues was classified into two major categories, those with less than 80% and those with more than 80% loss as compared to control. The results reveals that only the category with greater than 80% DA loss exhibited lower levels of ME in caudate and SP in putamen whereas no differences were observed in the levels of DYN in these regions. The frontal cortical region exhibited no changes in the levels of peptides. In other studies, experimental DA deficiency in rodents induced by neurotoxin such as 6-hydroxydopamine (6-OHDA) produced an increase in ME and a decrease in SP in basal ganglia. However, the levels of both peptides were lower in postmortem Parkinsonian basal ganglia in the present study. It appears that there is a DA-dependent, secondary loss of enkephalin and tachykinin peptides in PD. In view of the involvement of these peptidergic systems in the regulation of behaviour, movement, memory and other functions, derangements in these systems should be considered as additional factors in the progression of symptoms of PD.
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PMID:Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of postmortem parkinsonian brains. 171 Nov 65

The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N'-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 analogue, RX 77368 (pGlu-His-3,3'-dimethyl-ProNH2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 micrograms) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 micrograms) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 microgram, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic effects of intrathecal galanin on behavioural and biochemical markers of spinal motor function in adult rats. 171 12

The distribution of galanin-like immunoreactivity (GAL-LI) in the spinal cord of the cat was studied by use of indirect histochemistry and the peroxidase-antiperoxidase (PAP) technique. In the ventral horn GAL-immunoreactive (IR) axonal fibers and terminals were most frequent in the ventral part of the motor nucleus. The GAL-IR axons also contained 5-hydroxytryptamine (5-HT)-LI, and they disappeared after spinal cord transection. It was concluded that these GAL-IR fibers belong to the serotoninergic bublospinal pathway. In the medulla oblongata from normal cats, scattered GAL-IR cell bodies were encountered within the nucleus raphe obscurus and nucleus raphe pallidus. Electron microscopic observations revealed that the fine structure of the GAL-IR axonal boutons in the motor nucleus was similar to that of 5-HT-IR boutons with a varying number of immunoreactive large dense core vesicles. The postsynaptic element in all cases studied was a dendrite. A dense GAL-IR axonal plexus was found in the superficial laminae I-II of the dorsal horn. Coexistence was found between the GAL- and substance P-LI in fibers within the dorsal horn plexus. Spinal cord transection did not alter the pattern of GAL-LI in the dorsal horn, while the vast majority of GAL-IR axonal swellings disappeared following dorsal root sectioning. Electron microscopic observations in lamina II (substantia gelatinosa) revealed that the GAL-IR axonal terminals could be divided into two main groups. One with small to medium-sized axonal boutons formed synaptic contacts with both dendritic and axonal profiles. The other formed the central axon terminals of glomeruli, suggesting that GAL-LI may be present in C-type primary afferents. Numerous small GAL-IR cell bodies were encountered in laminae II and III. GAL-IR cell bodies were also observed in lamina X. The dorsal root ganglia contained a low but consistent number of small to medium-sized GAL-IR cell bodies, which all contained immunoreactive calcitonin gene-related peptide (CGRP). Following peripheral sciatic nerve transection, the number and the labeling intensity of GAL-IR cell bodies in the corresponding dorsal root ganglia showed a moderate increase. Radioimmunoassay revealed that the concentration of GAL-LI increased along the rostrocaudal axis of the normal spinal cord, and was about three times higher in the dorsal than in the ventral regions. The concentration in the dorsal root ganglia was intermediate to those seen in the corresponding dorsal and ventral cord regions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Distribution of 125I-galanin binding sites, immunoreactive galanin, and its coexistence with 5-hydroxytryptamine in the cat spinal cord: biochemical, histochemical, and experimental studies at the light and electron microscopic level. 171 21

Substance P (SP)- and 5-hydroxytryptamine (5-HT)-containing presynaptic boutons in the cervical ventral horn were studied in chicken, hamster, rat and monkey spinal cords, using PAP and protein A-gold double-labeling techniques in conjunction with monoclonal antibodies. In the chicken, the PAP method demonstrated that SP-immunoreactive boutons contained large spherical dense-cored vesicles (DCVs) whereas 5-HT-immunoreactive boutons displayed both elongated and spherical DCVs. Using the protein A-gold double-labeling technique, 10-nm gold particles for SP were localized over the spherical DCV-containing boutons whereas 15-nm gold particles for 5-HT were localized on elongated DCV-containing boutons. On the other hand, in the other species investigated, both SP- and 5-HT-immunoreactive boutons had similar morphological features as shown by the PAP method; both contained elongated and spherical DCVs. The two different sized gold particles, each of which labeled either 5-HT or SP, were found together over DCVs in a single bouton. These results indicate that 5-HT and SP are contained in different presynaptic boutons in the chicken, although in the hamster, rat and Japanese macaque, the two neurotransmitters/modulators coexist in the same DCVs in a single bouton. Species differences have thus been demonstrated for the coexistence of 5-HT and SP in the spinal ventral horn.
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PMID:Species differences in the coexistence of 5-hydroxytryptamine and substance P in presynaptic boutons in the cervical ventral horn. 171 39

Interactions between 5-hydroxytryptamine (5-HT) and substance P (SP) in the mouse spinal cord were investigated using the tail-flick test and the behavioral response evoked by intrathecal (i.th.) SP or i.th. 5-HT. I.th. injection of 5-HT (20 micrograms) or the 5-HT1 receptor agonists (+)-8-hydroxy-2-(di-n-propylamino)tetralin ((+)-8-OH-DPAT) (20 micrograms) or 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969) (20 micrograms) markedly inhibited the tail-flick reflex. The effect of these compounds was reduced when SP (5 micrograms) was given i.th. 55 min, or 55 and 45 min before the agonists. The tail-flick latencies recorded 5 min before injection of a 5-HT receptor agonist were similar in animals treated with SP or vehicle. The changes in the tail-flick test were not due to changes in tail skin temperature since only minimal differences in the skin temperature were recorded between the groups injected with SP or vehicle. I.th. injection of SP (10 ng) or 5-HT (2 micrograms) produced a similar behavioral response consisting of biting, licking and scratching of the caudal part of the body, indicative of nociceptive stimulation. The responses both to i.th. SP and 5-HT were reduced after i.th. application of the SP receptor antagonist [D-Arg1,D-Trp7.9,Leu11]-SP (Spantide) (5 micrograms), as well as 5 min after i.th. injection of the 5-HT receptor antagonist metergoline (4 micrograms). The data may indicate functional interactions between SP and 5-HT in the mouse spinal cord, which may take place in neurons involved in the processing of nociception.
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PMID:Interactions between serotonin and substance P in the spinal regulation of nociception. 171 3

5-HT3 receptors may be present on primary afferent neurons containing substance P (SP), neurokinin A (NKA) or calcitonin gene-related peptide (CGRP). We investigated the release of SP-, NKA- and CGRP-immunoreactivities (IR) from rat spinal cord slices. Thirty mM potassium chloride caused an increased outflow of all three peptides, i.e. 140-190% of spontaneous release. This release was slightly enhanced in the presence of 3 x 10(-5) M 5-hydroxytryptamine (5-HT). In contrast, a significant inhibition of potassium-evoked, but not of basal NKA-IR and CGRP-IR release was observed when 10(-7) M BRL 43694 or ICS 205-930, two specific 5-HT3 receptor antagonists, were superfused together with 5-HT. In conclusion, 5-HT may facilitate the evoked release of peptides from central terminals of primary sensory neurons via 5-HT3 receptors.
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PMID:5-HT3 receptor antagonists inhibit sensory neuropeptide release from the rat spinal cord. 171 37


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