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 vestibular end organs of the rabbit were fixed intracardially with phosphate buffered 4% formaldehyde, sectioned for 15 micron cryostat sections and incubated with monoclonal substance P (SP) antibody. Specific SP-like immunoreactivity (SPLI) was observed within and below the sensory epithelia of both utricular and saccular maculae and ampullary cristae. Particularly strong SPLI was seen in the maculae which showed many SPLI-positive axons in the subepithelial space and a network of SPLI-positive structures in the basal zones of the sensory epithelium. The calyceal terminals of type I hair cells showed regularly SPLI. The possibility of a transmitter or modulator role for SP in the vestibular function is suggested.
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PMID:Is substance P the neurotransmitter in the vestibular end organs? 620 37

The actions of substance P and eledoisin on contraction, [3H]inositol 1-phosphate and cAMP formation in the rat ileum have been compared. Eledoisin was considerably more potent than substance P on both contraction and [3H]inositol 1-phosphate production. Neither peptide altered the cAMP levels in the tissue. These results are discussed in relation to the substance P receptor sub-type present in the rat ileum, and its second messenger.
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PMID:The action of substance P on contraction, inositol phospholipids and adenylate cyclase in rat small intestine. 621 88

Cathepsin D was purified about 1000-fold from human brain cortex by a procedure involving ammonium sulfate fractionation (30-70%), Sephadex G-75 chromatography, affinity chromatography on pepstatin-Sepharose and isoelectric focusing. The enzyme was assayed fluorometrically at pH 3.2, the substrates used were globin or haemoglobin modified with pyridoxal-5'-phosphate. 6 multiple forms of cathepsin D were resolved in the isoelectric focusing step with pI values 4.4, 4.8, 5.3, 6.2, 6.5 and 6.8. Km of pyridoxal-globin and pyridoxal-haemoglobin for all 6 multiple forms is 1.8-2.0 X 10(-5) M and 1.3 to 4 X 10(-6) M, respectively, and Ki of pepstatin is 2-4 X 10(-9) M. Gel filtration of the multiple forms on Sephadex G-100 column showed that each has a molecular weight of about 50 000. Human brain cathepsin D has a pH optimum of 3.2 with a smaller second optimum at pH 4.0 (pyridoxal-haemoglobin being used as substrate). All the multiple forms have the same pH-dependence curve. On SDS-polyacrylamide gel electrophoresis the purified enzyme produced 3 bands approximately corresponding to Mr 50 000, 35 000 and 15 000. Study of the breakdown of substance P and its C-terminal heptapeptide by cathepsin D shows that cleavage occurs at the Phe-Phe linkages of both substrates tested.
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PMID:Cathepsin D from human brain: purification and multiple forms. 667 69

Human placenta is surprisingly rich in post-proline dipeptidyl peptidase activity. Among various cell fractions, microsomes have the highest specific activity. A homogeneous enzyme preparation is obtained in a six-step purification procedure. The final preparation appears homogeneous upon dodecyl sulfate electrophoresis, but analytical isoelectric focussing reveals various active bands with isoelectric points in the range of pH 3-4. The enzyme is a glycoprotein containing about 30% carbohydrate. Treatment with neuraminidase lowers the isoelectric points but does not reduce the heterogeneity of the band pattern. The subunit molecular weight is 120000 as estimated by dodecyl sulfate electrophoresis, whereas Mr of the native enzyme is greater than 200000, as can be concluded from gel filtration experiments. The purified dipeptidyl peptidase cleaves various synthetic and natural peptides, including substance P, kentsin, casomorphin and a synthetic renin inhibitor. In general, the specificity of the placenta peptidase is similar to that of post-proline dipeptidyl peptidase from other sources. Phenylalanylprolyl-beta-naphthylamide (Km = 0.02 mM, V = 92 U/mg) is the best substrate among various synthetic peptide derivatives. Only peptides with a free N-terminal amino group and proline, hydroxyproline, or alanine in position 2 of the N-terminal sequence are cleaved. However, X-Pro-Pro-. . . structures, e.g. as in bradykinin, are not attacked. 1 mM bis-(4-nitrophenyl)phosphate or 1 mM diisopropylfluorophosphate completely inactivate the peptidase within 30 min at 30 degrees C (pH 8). The peptidase is also completely inhibited by 1 mM Zn2+ and by other heavy metals.
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PMID:Isolation and characterization of dipeptidyl peptidase IV from human placenta. 675 24

Calmodulin (CaM) binding by turkey gizzard myosin light chain kinase (MLCK) causes subtle changes in the fluorescence emission and polarization excitation spectra of the enzyme. Fluorescence experiments using 9-anthroyl-choline (9AC), which competes with ATP in binding, demonstrate mutually stabilizing interactions between the CaM and ATP binding sites corresponding to delta G = -0.6 to -0.7 kcal/mol. Fluorescence titrations in the presence of 9AC or 5,5'-bis[8-(phenylamino)-1-naphthalenesulfonate] confirm the stoichiometry of 1 mol of CaM/MLCK. Phosphorylation of MLCK has no effect on either the protein fluorescence or the binding of ATP and 9AC. The dissociation constant for the MLCL-CaM complex is increased approximately 500-fold on phosphorylation. Values of Kd for the phosphorylated enzyme range from 0.5 to 1.1 microM in 0.2 N KCl, pH 7.3, 25 degrees C. We showed competition between MLCK and other CaM binding proteins and peptides by using both fluorescence and catalytic activity measurements. Competition for CaM occurs with ACTH, beta-endorphin, substance P, glucagon, poly(L-arginine), myelin basic protein, troponin I, and histone H2A. Phosphorylation of the last three proteins by the adenosine cyclic 3',5'-phosphate dependent protein kinase diminishes their ability to compete. Phosphorylation of MLCK by the protein kinase gives 0.95 +/- 0.04 and 2.2 +/- 0.4 mol of incorporated 32P in the presence and absence of CaM, respectively. These stoichiometries agree with those recently reported [Conti, M. A. & Adelstein, R. S. (1981) J. Biol. Chem. 256, 3178].
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PMID:Functional interactions between smooth muscle myosin light chain kinase and calmodulin. 689 95

This study investigated the cholinesterasic reactivity of catecholamine neurons in the rat hindbrain with the aid of a two-step histochemical procedure. First, catecholamine cells were visualized by their formaldehyde/glutaraldehyde induced specific histofluorescence and then poststained in the same tissue with a thiocholine technique for acetylcholinesterase (AChE). Processing the vibratome-sectioned tissue in phosphate buffer subsequent to initial aldehyde fixation permitted satisfactory preservation of both amine fluorophores and esterasic reactivity. Our results, in both randomly sampled and serially sectioned material, unequivocally establish the presence of AChE in all pontomedullary cell groups emitting catecholamine fluorescence, the majority of which are known to consist of noradrenaline perikarya. Hence in contrast to previous reports the occurrence of AChE in central noradrenaline neurons appears to be generalized. The intensity of histofluorescence and esterasic staining were uncorrelated in most regions. It remains for future study to determine whether AChE in brain catecholamine neurons indicates their cholinoceptivity or subserves the catabolism of other neuromediators such as substance P.
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PMID:Acetylcholinesterase in pontomedullary catecholamine neurons of the adult albino rat. 706 9

1. The effect of Li+ on the agonist-dependent metabolism of [3H]inositol has been studied in rat brain, rat parotid and the insect salivary gland. 2. When brain or parotid slices were incubated in the presence of [3H]inositol, Li+ was found to amplify the ability of agonists such as carbachol, phenylephrine, histamine, 5-hydroxytryptamine and Substance P to elevate the amount of label appearing in the inositol phosphates. 3. A different approach was used with the insect salivary gland, which was prelabelled with [3H]inositol. After washing out the label, the subsequent release of [3H]inositol induced by 5-hydroxytryptamine was greatly decreased by Li+. During Li+ treatment there was a large accumulation of [3H]inositol 1-phosphate. 4. This ability of Li+ to greatly amplify the agonist-dependent accumulation of myo-inositol 1-phosphate offers a novel technique for identifying those receptors that function by hydrolysing phosphatidylinositol. 5. The therapeutic action of Li+ may be explained by this inhibition of myo-inositol 1-phosphatase, which lowers the level of myo-inositol and could lead to a decrease in the concentration of phosphatidylinositol, especially in those neurons that are being stimulated excessively. This alteration in phosphatidylinositol metabolism may serve to reset the sensitivity of those multifunctional receptors that generate second messengers such as Ca2+, cyclic GMP and the prostaglandins.
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PMID:Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. 715 Feb 64

Nitric oxide synthase-like immunoreactivity was found in a subpopulation of sympathetic postganglionic neurons in the cat stellate and lower lumbar ganglia. In the ganglia of other segments such cells were rare. Double staining for tyrosine hydroxylase-like immunoreactivity and nitric oxide synthase-like immunoreactivity or the reduced nicotinamide adenine dinucleotide phosphate diaphorase reaction indicated that nitric oxide synthase-like immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase reactivity was always co-localized and was confined to tyrosine hydroxylase-negative (presumably cholinergic) ganglion cells, and was present in most of them. The occurrence of nitric oxide synthase in two subpopulations of cholinergic postganglionic neurons was investigated in triple staining experiments. Presumptive sudomotor neurons have been previously defined as scattered cells containing calcitonin gene-related peptide-like immunoreactivity, usually accompanied by vasoactive intestinal peptide-like immunoreactivity: 99% of these contained nitric oxide synthase. Presumptive muscle vasodilator neurons have been previously identified as clumped cells with strong vasoactive intestinal peptide-like immunoreactivity but no calcitonin gene-related peptide-like immunoreactivity: 70% of these contained nitric oxide synthase. Sweat glands were found in the paw pad skin surrounded by varicose fibres showing calcitonin gene-related peptide-like immunoreactivity and vasoactive intestinal peptide-like immunoreactivity, confirming previous work. Such fibres also stained for nitric oxide synthase-like immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase reactivity, although their staining was relatively weaker than in the corresponding cell bodies. Varicose fibres with the same chemical coding were also found around all large and most medium and small arteries in the paw skin as well as around arteriovenous anastomoses. Fibres with the muscle vasodilator coding (vasoactive intestinal peptide-like immunoreactivity without calcitonin gene-related peptide-like immunoreactivity) were not seen in paw skin. These results suggest that nitric oxide may act as a co-transmitter (with acetylcholine, substance P, vasoactive intestinal peptide and calcitonin gene-related peptide) in sudomotor neurons and (with acetylcholine and vasoactive intestinal peptide) in vasodilator neurons. Collateral branches of sudomotor neurons may innervate skin vessels, and release vasodilator transmitters including nitric oxide to cause the vasodilatation which provides the fluid supply for sweat formation. Alternatively, separate vasodilator neurons to skin may share the same chemical code as sudomotor neurons.
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PMID:Nitric oxide synthase and chemical coding in cat sympathetic postganglionic neurons. 747 30

The carotid body is an arterial chemoreceptor organ sensitive to blood levels of O2, CO2 and pH. The present immunocytochemical and neurochemical study has demonstrated the presence of an extensive plexus of nitric oxide (NO)-synthesizing nerve fibers in this organ. These nitric oxide synthase (NOS)-containing axons are closely associated with parenchymal type I cells and with blood vessels in the carotid body. Denervation and retrograde tracing experiments have revealed that these fibers arise from NOS-immunoreactive and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neuronal cell bodies located in the petrosal ganglion and the carotid body, and dispersed along the glossopharyngeal and carotid sinus nerves (CSN). Within the petrosal ganglion, these neurons are topographically segregated from the catecholaminergic cells, and they contain the neuropeptide, substance P. NOS-positive autonomic microganglial cells in the carotid body and CSN also exhibit choline acetyltransferase (ChAT) immunoreactivity. Our results suggest that nitric oxide may be a novel neuronal messenger in the mammalian carotid body involved in the modulation of chemosensory transduction and transmission in this organ.
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PMID:Neurons synthesizing nitric oxide innervate the mammalian carotid body. 750 96

The hexapeptide [pGlu6,Pro9]substance P (SP)6-11, septide, has been shown to be an agonist as potent as SP in eliciting smooth muscle contraction in several in vitro preparations, while being a poor competitor of labeled SP binding. These results, as well as other pharmacological data, have suggested the existence of either a specific septide receptor or a septide site on the neurokinin (NK)1 receptor distinct from that for SP. We have used rat recombinant NK1 receptor expressed in COS-1 cells to address this issue. Both functional (agonist-induced inositol phosphate accumulation) and radioligand binding studies were conducted on transiently transfected cells. SP and septide elicited similar maximal increases (4-6-fold) in inositol phosphate levels in transfected cells, with EC50 values of 0.05 +/- 0.02 nM for SP and 5 +/- 2 nM for septide. No additivity of the maximal responses to the two agonists was observed, and neither agonist evoked any response in sham-transfected cells. RP 67580 was a competitive inhibitor of SP responses, with an inhibition constant (KB) of 13 +/- 2 nM, in agreement with displacement studies of [3H]SP binding to membranes and intact transfected cells (Ki values of 10 +/- 4 nM, and 1.16 +/- 0.06 nM, respectively). In comparison, septide responses were inhibited by RP 67580 in an uncompetitive fashion, with an apparent KB* value of 1.5 +/- 0.2 nM. Septide was a weak competitor of [3H]SP binding, with dissociation constants (Ki) of 2.9 +/- 0.6 microM and 3.7 +/- 0.9 microM for membranes and intact transfected cells, respectively. Similarly, septide at concentrations up to 10 microM did not affect [3H]RP 67580 binding. In conclusion, we have demonstrated that septide is a potent functional agonist of the NK1 receptor but it seems to act at a specific subsite different from that for SP. Although not ruling out the existence of selective septide receptors in some tissues, these results could explain some of the discrepancies with regard to the pharmacological properties of septide. Furthermore, a specific septide site on the NK1 receptor could represent an original pharmacological target.
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PMID:Septide: an agonist for the NK1 receptor acting at a site distinct from substance P. 750 40


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