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)

Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.
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PMID:Effect of synthetic substance P on monoaminergic mechanisms in brain. 0 76

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

The pharmacological specificity of the GABA agonist muscimol-induced contralateral turning behavior after unilateral injection into substantia nigra pars reticulata (SNR) has been studied. Muscimol-induced turning was antagonized by intranigral bicuculline methochloride (BMC) and picrotoxin, whereas antagonists of glycine, morphine, dopamine, noradrenaline, and serotonin were ineffective. Glycine induced a qualitatively similar turning behavior which was strychnine-sensitive but relatively BMC and picrotoxin-insensitive. Other drugs, including substance P, kainic acid, clonidine, oxymetazoline, serotonin, and carbachol, induced turning that could be dissociated from the effect of muscimol. Muscimol-induced turning was dopamine-independent, indicated by resistance to haloperidol (1 mg/kg), to pretreatment with reserpine (7.5 mg/kg) plus alpha-methyl-p-tyrosine (200 mg/kg), to haloperidol injections into the SNR, striatum and nucleus accumbens, and finally to kainic acid lesions of the striatum. 6-Hydroxydopamine lesions increased the efficacy of intranigral muscimol, while kainic acid lesions of the SNR antagonized muscimol. Muscimol-induced turning was inhibited by oxotremorine (0.25 mg/kg), by intranigral carbachol, and by apomorphine (0.1--0.5 mg/kg), but only moderately by intranigrally injected apomorphine. These data suggest specificity of GABA-agonist-induced contralateral turning and indicate an interaction between nigral GABA and other neurotransmitters, particularly dopamine and acetylcholine.
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PMID:GABAergic and glycinergic mechanisms within the substantia nigra: pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters. 3 44

Acetylcholine (ACh) (10(-5) M) in the presence of eserine (2 . 10(-4) M) stimulated the release of [3H]dopamine (DA) continuously formed from [3H]tyrosine, when delivered to a push-pull cannula implanted in the left caudate nucleus of halothane anaesthetized cats. This effect was transient and followed by a second increase in [3H]DA release after removal of ACh and eserine. These changes in [3H]DA release during and after ACh application were no longer seen during activation of the dopaminergic neurons by continuous delivery of substance P to the ipsilateral substantia nigra (SN). These results indicate that the presynaptic regulation of DA release by ACh is dependent on the rate of firing of nigro-striatal dopaminergic neurons.
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PMID:The presynaptic stimulating effect of acetylcholine on dopamine release is suppressed during activation of nigro-striatal dopaminergic neurons in the cat. 9 24

The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone "C" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function.
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PMID:[Chemistry and biology of hypothalamic cardioactive proteins and peptides]. 22 93

The indirect immunofluorescence method and the unlabeled primary antibody peroxidase antiperoxidase method are used to demonstrate the substance P (SP) plexus in the spinal cord and SP cells in the sensory ganglia of the rat. The normal untreated and the control side of the dorsal rhizotomized rat show vast SP immunoreactive plexuses in the substantia gelatinosa, central gray, and ventral gray regions of the spinal cord. In each sensory ganglion, approximately 250 SP immunoreactive cells are found singly or in small groups of 2 or 3, near blood capillaries or among ganglion and satellite cells. They contain intensely immunoreactive cytoplasmic granules 0.1-3.0 mum across. Occasionally, free intensely immunoreactive granules are found in the surrounding tissue near an SP cell but not clearly within the confines of the cell. Another type of immunoreaction has been observed with both methods. A less intense, homogeneous reactivity has been found in lamellae insinuated between ganglion cells and near blood capillaries close to an SP cell; the characteristic disposition of this homogeneous reactivity suggests an extracellular location. Unilateral rhizotomy results in an increased number of immunoreactive SP cells and nerve fibers as well as a more extensive homogeneous immunoreactivity. These results add to existing evidence that SP cells in sensory ganglia send fibers via the dorsal roots to the spinal cord. SP cells, fibers, and terminals do not take up exogenously applied (125)I-labeled [Tyr(8)]SP and cannot be demonstrated by subsequent autoradiography. No neurotensin immunoreactive cells were found in sensory ganglia.
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PMID:Immunocytochemical identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord: light microscopic studies. 33 42

A new devised arginine derivative, NG-mesitylene-2-sulfonylarginine, Arg(Mts), was employed for the synthesis of hypothalamic substance P and neurotensin. The former was obtained in 74% yield by treatment of the protected undecapeptide amide, Z - Arg(Mts) - Pro - Lys(Z) - Pro - Gln - Gln - Phe - Phe - Gly - Leu - Met(O)-NH2, with methanesulfonic acid in the presence of anisole followed by reduction of the sulfoxide with 2-mercaptoethanol. The latter was obtained in 54% yield by the similar treatment of the protected tridecapeptide ester, Z - Pyr - Leu - Tyr - Glu(OBzl) - Asn - Lys(Z) - Pro - Arg(Mts) - Arg(Mts) - Pro - Tyr - Ile - Leu - OBzl, with methanesulfonic acid. As scavenger, a mixture of anisole-thioanisole-o-cresol (1:1:1, by vol.) was employed to suppress the side reaction, O-mesitylene-2-sulfonation of the Tyr residue.
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PMID:Studies on peptides. LXXXI. Application of a new arginine derivative, NG-mesitylene-2-sulfonylarginine, to the synthesis of substance P and neurotensin. 48 55

Secretin, substance P, and vasoactive intestinal peptide (VIP) were studied from the immunological point of view using synthetic hormones and their related peptides which were prepared by the conventional method for peptide synthesis. Immunological properties of these hormones were characterized by radioimmunoassays specific to the respective hormones. Antisecretin antisera (NCC-R-1 and R-801) were generated in rabbits with synthetic porcine secretin absorbed on polyvinylpyrrolidone. Antiserum to substance P (R-400) was produced in a rabbit with synthetic substance P-human alpha-globulin conjugate. Generation of anti-VIP antiserum (R-502) was carried out by immunizing rabbits with synthetic VIP absorbed on polyvinylpyrrolidone. Synthetic polypeptides related to the three hormones that were examined in this study include secretin(4-27), secretin(5-27), secretin(7-27), secretin(11-27), secretin(14-27), secretin(18-27), secretin(1-22)amide, secretin(7-22)amide, Nalpha-tyrosyl-secretin, [1-Tyr]secretin, [4-Ala]secretin, [4-D-Ala]secretin, [4-Ala,5-Val]secretin, [6-Tyr]secretin, substance P(2-11), substance P (3-11), substance P(4-11), substance P(5-11), substance P(6-11), Nalpha-tyrosyl-substance P, [1-Tyr]substance P, [8-Tyr]substance P, [11-Leu]substance P, des-11-Met-substance P, VIP(7-28), VIP(11-28), VIP(18-28), VIP(1-18)amide, and VIP(1-22)AMIDE. The results revealed two antigenic regions at the amino- and carboxylterminal portions of the secretin and VIP molecules. As to substance P, the major antigenic region was located within the 3 to 11 sequence. The proline residue in position 4 and methionine in position 11 seemed to be of special importance. The immunoassays demonstrated the existence of immunoreactivities of these hormones in hot water extracts from various porcine tissues. In the pituitary, VIP and substance P immunoreactivities were detected, whereas secretin was not. Secretin, VIP, and substance P were found in the pancreas, but at low concentrations. Distributions of these hormones in various sites of the gastrointestinal tract were also demonstrated.
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PMID:Immunological aspects of secretin, substance P, and VIP. 83 40

[Tyr8]-substance P, an undecapeptide having the structure Arg-Pro-Lys-Pro-Gln-Gln-Phe-Tyr-Gly-Leu-Met-NH2, has been synthesized by the solid-phase technique on a Beckman automatic peptide synthesizer, appropriately purified and biologically characterized. At twice the dosage, [Tyr8]-substance P showed the same biological activity response as synthetic substance P for stimulation of contraction of the isolated guinea pig ileum and for decrease in the systemic blood pressure of dogs. On the dog's blood pressure, no qualitative differences were observed, but on the isolated gut, the Tyr8 analog gave a more gradual increase in the muscle tone than synthetic substance P. [Tyr8]-substance P released, in vitro, the luteinizing and follicle-stimulating hormones at a very high dosage but did not release growth hormone, prolactin, or thyrotropin.
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PMID:Synthesis and some biological activities of the tyrosine-8 analog of substance P. 124 14

Using a sensitive in vitro microperfusion method, the effects of selective and potent agonists of NK1, NK2, and NK3 tachykinin receptors ([Pro9]SP, ([Lys5,MeLeu9,Nle10]NKA-(4-10), and [Pro7]NKB, respectively) on the presynaptic control of dopamine release were investigated in striosomal-enriched (area rich in [3H]naloxone binding sites) and matrix-enriched areas of the rat striatum. Marked differences could be demonstrated as follows: (i) when used at 0.1 microM, the NK1 agonist stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both compartments, while the NK2 and NK3 agonists enhanced the release of [3H]dopamine only in the matrix; (ii) the stimulatory effect of the NK3 agonist was less pronounced than those of the NK1 and NK2 agonists; (iii) the NK1 agonist-evoked responses were tetrodotoxin (1 microM) sensitive, while those of the NK2 and NK3 agonists were, respectively, partially and totally tetrodotoxin resistant; (iv) specific receptors are involved in these responses since the stimulatory effects of the NK1 and NK2 agonists were, respectively, blocked by potent antagonists of NK1 (RP-67580; 1 microM) and NK2 (SR-48968; 1 microM) receptors, while these antagonists did not affect the NK3 agonist-evoked response; (v) the indirect stimulatory effect of the NK1 agonist was partially reduced under local blockade of cholinergic transmission in the matrix but not in the striosomal-enriched area. Interestingly, this study also revealed mismatches between autoradiographic data and receptor-mediated responses, since NK2 binding sites could not be observed in the striatum while NK3 but not NK1 binding sites were visualized in the striosomal-enriched area.
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PMID:Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. 128 Aug 22


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