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)

Cumulative contractile response curves to neurokinin A (NKA) and neuropeptide gamma (NP gamma) were obtained in human isolated bronchus, in the presence of phosphoramidon 10 microM. NP gamma was approximately 10-fold more potent than NKA (pD2 values 8.6 +/- 0.4 and 7.3 +/- 0.3 respectively, n = 6; P less than 0.01). The NK1-selective agonist [Sar9, Met(O2)11]-SP and the NK3 selective agonist senktide produced negligible contraction. Response curves to NP gamma and NKA were unaffected by the NK2 subtype-selective antagonist MDL 29913 at 2 microM, but NP gamma-induced contraction was markedly inhibited by 20 microM MDL 29,913. Thus NP gamma is the most potent tachykinin in human isolated bronchus and its effects are mediated at a receptor which is not of the 'classical' NK2 subtype found in hamster urinary bladder.
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PMID:Neuropeptide gamma, the most potent contractile tachykinin in human isolated bronchus, acts via a 'non-classical' NK2 receptor. 166 97

The effects of selective NK-1, NK-2 and NK-3 tachykinin agonists in midbrain dopamine cell containing regions were investigated in the rat. The NK-3 agonist senktide induced locomotion, rearing and sniffing following infusion into the substantia nigra pars compacta, and to a lesser extent in the ventral tegmental area. These behavioural responses were not seen following infusion of the selective NK-1 agonist [Sar9,Met (O2)11]SP or the NK-2 agonist [N1e10]NKA4-10. In contrast, grooming was induced only by the NK-1 agonist administered into the substantia nigra. Yawning, chewing mouth movements and wet dog shakes were all seen following infusion of senktide into the ventral tegmental area. These findings suggest that (i) dopamine-mediated behavioural responses seen following tachykinin administration into the midbrain are dependent upon stimulation of NK-3 tachykinin receptors, (ii) tachykinin-induced grooming is mediated by stimulation of NK-1 receptors and (iii) some of the previously described 5-HT mediated behaviours seen following administration of NK-3 tachykinin agonists are probably generated by stimulation of 5-HT cell bodies in the ventral tegmental area.
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PMID:Behavioural effects of selective tachykinin agonists in midbrain dopamine regions. 166 12

A membrane-bound enkephalin-degrading aminopeptidase was purified from the longitudinal muscle layer of the guinea pig small intestine by four steps of column chromatography using L-tyrosine beta-naphthylamide. The molecular weight of the enzyme was estimated to be 105,000 by gel filtration. The maximum activity was observed between pH 6.5 and 7.0. The Km value for leucine-enkephalin was 137 microM. The aminopeptidase activity toward aminoacyl beta-naphthylamide substrates was restricted to basic, neutral, and aromatic aminoacyl derivatives. No action was detected on acidic amino acid and proline derivatives. The enzyme was potently inhibited by the aminopeptidase inhibitors actinonin, amastatin, and bestatin, and bioactive peptides such as angiotensin III, substance P, and Met-Lys-bradykinin. The enzyme activity was also inhibited by the antibody against the purified serum enkephalin-degrading aminopeptidase of guinea pig at concentrations similar to those at which activity was observed toward serum enkephalin-degrading aminopeptidase and renal aminopeptidase M. The enzyme rapidly hydrolyzed Leu-enkephalin and Met-enkephalin with the sequential removal of the N-terminal amino acid residues. The enzyme also hydrolyzed two enkephalin derivatives, angiotensin III and neurokinin A. However, neurotensin, substance P, and bradykinin were not cleaved. These properties indicated that the membrane-bound enkephalin-degrading aminopeptidase in the longitudinal muscle layer of the small intestine is similar to the serum enkephalin-degrading aminopeptidase and resembles aminopeptidase M. It is therefore suggested to play an important role in the metabolism of some bioactive peptides including enkephalin in peripheral nervous systems in vivo.
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PMID:Enkephalin-degrading aminopeptidase in the longitudinal muscle layer of guinea pig small intestine: its properties and action on neuropeptides. 167 58

Results reported here confirm and extend those of early retrograde transport studies of the brainstem in the rat and cat. This study demonstrates substantial and multiple afferent projections to the cat locus coeruleus arising from neurons containing acetylcholine, serotonin, norepinephrine, epinephrine, dopamine, histamine, and neuropeptides such as methionine, enkephaline and substance P. Further, our studies reveal notable differences in afferent projection to the noradrenergic and cholinergic regions of the locus coeruleus.
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PMID:Physiological properties and afferent connections of the locus coeruleus and adjacent tegmental neurons involved in the generation of paradoxical sleep in the cat. 168 20

We have shown previously that some enkephalin, substance-P, and serotoninergic neurons in the medullary raphe and adjacent reticular formation project to the spinal cord in the opossum. In the present study we have combined the retrograde transport of True Blue and immunofluorescence histochemistry to determine whether methionine enkephalin or substance-P containing bulbospinal neurons are serotoninergic. Furthermore, we have used the same immunofluorescence protocol to determine whether spinal axons contain the same substances. Neurons that immunostained for both enkephalin and serotonin were observed in many brainstem nuclei. However, those that projected to the spinal cord were limited to the nuclei raphe magnus and obscurus, and the ventral part of nucleus reticularis gigantocellularis, pars ventralis. Neurons that immunostained for both substance P and serotonin were fewer in number, but some of the ones in the above nuclei and within the nucleus raphe pallidus, projected to the spinal cord. Spinal axons exhibiting both enkephalin- and serotonin-like immunoreactivity were observed in the superficial laminae of the dorsal horn, lamina X, and the intermediolateral cell column, whereas those showing both substance-P and serotonin-like immunoreactivity were seen primarily in lamina X, the intermediolateral cell column, and the ventral horn. Some of the axons in the ventral horn were in close apposition to presumed motoneurons. Comparison of the above results with those obtained from previous studies of bulbospinal projections has allowed us to infer the origins of axons that innervate different spinal targets.
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PMID:Origins and terminations of bulbospinal axons that contain serotonin and either enkephalin or substance-P in the North American opossum. 169 Dec 16

A number of different neuroactive substances have been found in striatal projection neurons and in fibers and terminals in their target areas, including substance P (SP), enkephalin (ENK), and dynorphin (DYN). In a preliminary report on birds and reptiles, we have suggested that SP and DYN are to a large extent found in the same striatal projection neurons and that ENK is found in a separate population of striatal projection neurons. In the present study, we have examined this issue in more detail in pigeons and turtles. Further, we have also explored this issue in rats to determine whether this is a phylogenetically conserved feature of basal ganglia organization. Simultaneous immunofluorescence double-labeling procedures were employed to explore the colocalization of SP and DYN, SP and ENK, and ENK and DYN in striatal neurons and in striatal, nigral, and pallidal fibers in pigeons, turtles, and rats. To guard against possible cross-reactivity of DYN and ENK antisera with each others' antigens, separate double-label studies were carried out with several different antisera that were specific for DYN peptides (e.g., dynorphin A 1-17, dynorphin B, leumorphin) or ENK peptides (leucine-enkephalin, metenkephalin-arg6-gly7-leu8, methionine-enkephalin-arg6-phe7). The results showed that SP and DYN co-occur extensively in specific populations of striatal projection neurons, whereas ENK typically is present in different populations of striatal projection neurons. In pigeons, 95-99% of all striatal neurons containing DYN were found to contain SP and vice versa. In contrast, only 1-3% of the SP+ striatal neurons and no DYN neurons contained ENK. Similarly, in turtles, greater than 75% of the SP+ neurons were DYN+ and vice versa, whereas ENK was observed in fewer than 5% of the SP+ neurons and 2% of the DYN+ neurons. Finally, in rats, more than 70% of the SP+ neurons contained DYN and vice versa, but ENK was found in only 5% of the SP+ neurons and in none of the DYN+ perikarya. Fiber double-labeling in the striatum and its target areas (the pallidum and substantia nigra) was also consonant with these observations in pigeons, turtles, and rats. These results, in conjunction with studies in cats by M.-J. Besson, A.M. Graybiel, and B. Quinn (1986; Soc Neurosci. Abs. 12:876) strongly indicate that the co-occurrence of SP and DYN in large numbers of striatonigral and striatopallidal projection neurons in a phylogenetically widespread, and therefore evolutionarily conserved, feature of basal ganglia organization.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extensive co-occurrence of substance P and dynorphin in striatal projection neurons: an evolutionarily conserved feature of basal ganglia organization. 169 32

1. We have used pharmacologic, immunologic, and biochemical techniques to examine the role of neurochemicals in modulating the myogenic heart of the snail, Lymnaea. 2. 5-HT [high-pressure liquid chromatography (HPLC) and immunocytochemistry], dopamine (HPLC), FMRFamide-related peptides (radioimmunoassay and immunocytochemistry) and substance P-related peptides (immunocytochemistry) were shown to be localized within heart tissue. 3. The pharmacologic actions of these substances on the auricle from an isolated heart preparation were examined together with other putative modulators, acetylcholine (ACh), small cardioactive peptides A and B (SCPA and SCPB), [Arg]8vasotocin (AVT), and Lymnaea native FMRFamide-related peptides [Phe-Met-Arg-Phe-NH2 (FMRFamide), Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (SDPFLRFamide) and Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRFamide)]. 4. The response to each substance could be distinguished by different effect on beat rate, amplitude, and diastolic tonus, as well as by the duration of responses to standard 1-min applications. ACh was inhibitory at low concentrations (threshold less than 10(-10) M) but excitatory at high concentrations (10(-6) M). AVT was alone in producing no dose-dependent response. At high concentrations (10(-4) M), AVT caused a massive tonic contraction and cessation of auricle beat. All other substances examined were excitatory. 5. Antagonists to 5-HT (cinanserin), dopamine (ergonovine), and ACh (alpha-bungarotoxin) were identified. 6. ACh, 5-HT, dopamine, and FMRFamide-related peptides all acted on the auricle at low concentrations, and the rapid onset and short duration of their excitatory effects (ACh inhibitory at low concentrations) suggested that they may have roles as neurotransmitters. SCPA and SCPB were also potent (threshold less than 10(-10) M) but produced long-duration responses suggesting a modulatory or hormonal role.
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PMID:Pharmacology of the myogenic heart of the pond snail Lymnaea stagnalis. 169 38

A comparative topographical immunohistochemical analysis was performed on the basal ganglia (including the substantia nigra) in Guamanian parkinsonism-dementia complex, idiopathic Parkinson's disease (PD), and Alzheimer's disease (AD). The striatal projection neurons and their efferent fibers were examined by using antibodies to calcineurin, methionine-enkephalin, and substance P. Tyrosine hydroxylase served as a marker for nigrostriatal dopaminergic neurons. The basal ganglia of patients with parkinsonism-dementia complex reacted strongly with all of the antibodies and the reaction products exhibited a normal distribution pattern. These findings suggest that the striatal output system is well preserved in patients with this disease. Similar results were obtained in patients with AD or PD. However, as compared to the patients with AD or PD, patients with parkinsonism-dementia complex showed severe reduction (greater than 90%) in the number of dopaminergic neurons in both the lateral and the medial portions of the substantia nigra. In view of the functional cortico-subcortical loops, these findings could explain the parkinsonian features and in part the cognitive impairment that occur in parkinsonism-dementia complex on Guam.
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PMID:Immunohistochemical study of the striatal efferents and nigral dopaminergic neurons in parkinsonism-dementia complex on Guam in comparison with those in Parkinson's and Alzheimer's diseases. 169 18

1. The binding properties and pharmacological specificity of the selective NK3 tachykinin receptor agonist [3H))-senktide [( 3H]-succinyl[Asp6,MePhe8] substance P (6-11] have been examined in homogenates of guinea-pig ileum longitudinal muscle-myenteric plexus (LM/MP) and cerebral cortex. 2. Scatchard analysis of saturation binding studies in guinea-pig ileum LM/MP and cerebral cortex membranes indicated that [3H]-senktide bound to a single site with apparent high affinity, KD = 2.21 +/- 0.65 nM; Bmax = 13.49 +/- 0.04 fmol mg-1 protein in ileum and KD = 8.52 +/- 0.45 nM; Bmax = 76.3 +/- 1.6 fmol mg-1 protein in cortex (values are means +/- ranges; n = 2). 3. The pharmacological profile for tachykinins and analogues in displacing [3H]-senktide from ileum membranes was: [MePhe7] neurokinin B greater than neurokinin B (NKB) congruent to senktide greater than eledoisin greater than substance P (SP) greater than neurokinin A(NKA) greater than physalaemin greater than [Sar9,Met(O2)11]SP greater than [Nle10]NKA(4-10) = [Glp6,L-Pro9]-SP(6-11) greater than substance P methyl ester, consistent with [3H]-senktide binding to an NK3 subtype of tachykinin receptor. A similar rank order of affinity was obtained for these peptides in displacing [3H]-senktide from cortex membranes. 4. Several tachykinin receptor agonists were tested for their ability to displace [3H]-senktide from ileal and cortical NK3 binding sites and were found to be either weak displacers (pIC50 less than 5.00) or inactive. 5. The binding of [3H]-senktide to cortex membranes was inhibited by GTP (p1C,0 = 6.49)and GTP-gamma- S (p1C,0 = 6.67) with ATP being at least three orders of magnitude less potent (pIC50 = 3.55). 6. These results indicate that both central and peripheral NK3 receptors share a similar pharmacological specificity and that they may be labelled selectively with the NK3 receptor agonist [3H]-senktide.
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PMID:Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes. 169 64

Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.
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PMID:Degradation of airway neuropeptides by human lung tryptase. 169 72


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