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. Tachykinin-stimulated inositol phospholipid hydrolysis was examined in slices of longitudinal muscle from guinea-pig ileum. 2. Substance P, neurokinin A and neurokinin B induced a concentration-dependent accumulation of total [3H]-inositol phosphates in the presence of 12 mM lithium with similar maximal responses and EC50 values. 3. The selective NK1-receptor agonist, substance P methyl ester, and the selective NK3-receptor agonist succ-[Asp6, MePhe8]-SP(6-11) (senktide) also stimulated [3H]-inositol phosphate formation with maximum responses of 50.69 +/- 0.96 and 45.64 +/- 1.17% relative to 10 microM substance P, respectively. Substance P methyl ester was approximately equipotent with substance P, whereas senktide was approximately 100 times more potent. 4. When added together, maximally effective concentrations of substance P methyl ester and senktide gave responses that were fully additive. In contrast, responses to substance P and neurokinin B were not additive. 5. The stimulation of [3H]-inositol phosphate formation by substance P, neurokinin B and senktide was not affected by atropine (2 microM) or tetrodotoxin (TTX, 0.3 microM). 6. The contractile effect of senktide was inhibited completely by TTX and partially blocked by atropine. Contractions induced by substance P methyl ester were not changed in the presence of TTX or atropine. 7. [D-Pro4, D-Trp7,9,10]-SP(4-11) competitively antagonized the action of substance P methyl ester on inositol phospholipid hydrolysis and contraction, but had no significant effect on senktide-induced inositol phospholipid breakdown or contraction. 8. These results suggest that NK3-receptors in the guinea-pig ileum are coupled to inositol phospholipid hydrolysis.
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PMID:Neurokinin3-receptors are linked to inositol phospholipid hydrolysis in the guinea-pig ileum longitudinal muscle-myenteric plexus preparation. 245 6

Static muscular contraction has been shown to increase cardiovascular and ventilatory function in reflex manner. The sensory arm of this reflex arc is comprised of group III and IV muscle afferents. The discharge properties of these muscle afferents whose activation causes the pressor reflex response to contraction were investigated. Group III afferents were more responsive to mechanical stimuli, such as tendon stretch and probing their receptive fields than were group IV afferents. In contrast, group III afferents were less responsive to ischemic contraction than were group IV afferents. Equal percentages of group III and IV afferents were stimulated by potassium, lactic acid and arachidonic acid, each of which are metabolic products of contraction. Adenosine, phosphate and lactate, however, had no effect on the discharge of the afferents. Intrathecal injection of antagonists or antibodies to substance P and somatostatin attenuated the pressor response to contraction by about half, a finding that suggests a role for these 2 peptides in the spinal transmission of the reflex.
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PMID:Pressor reflex response to static muscular contraction: its afferent arm and possible neurotransmitters. 245 28

The two mammalian neuropeptides substance P (SP) and neurokinin A (NKA) have been demonstrated to stimulate DNA synthesis in connective tissue cells, suggesting that peripheral neurons may play a role in development and tissue regeneration. In this study we have tried to identify intracellular messengers required for SP- and NKA-induced DNA synthesis. SP and NKA, as well as platelet-derived growth factor (PDGF) stimulated formation of inositol phosphates in smooth muscle cells (SMC), whereas no effect on inositol phosphates formation occurred in response to nonmitogenic neuropeptides. Pretreatment of the cells with pertussis toxin markedly decreased DNA synthesis induced by NKA. This toxin inhibits formation of inositol phosphates by acting on a regulatory G-protein. Calcium and calmodulin antagonists also inhibited NKA-induced DNA synthesis. These results imply that the mitogenic signal(s) produced by activated neuropeptide receptors involves formation of inositol phosphate and activation of a calcium/calmodulin dependent process. We further report that other neuropeptides occurring in peripheral neurons, i.e., vasoactive intestinal polypeptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, or cholecystokinin, are without growth-stimulatory effect on cultured SMC.
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PMID:Coupling between inositol phosphate formation and DNA synthesis in smooth muscle cells stimulated with neurokinin A. 245 38

The effects of substance P (SP) on smooth-muscle contractions induced by noradrenaline (NA) or by high- or low-frequency electrical stimulation (ES) were studied on isolated rat vas deferens and musculus anococcygeus. Neither the contractile effects of NA nor those of high-frequency ES were significantly changed by SP. The peptide in concentrations of 1 x 10(-7) M and 1 x 10(-6) M strongly potentiated (up to 70%) vas deferens contractions in response to low-frequency ES but slightly reduced those of musculus anococcygeus. Inhibition of the opiate receptors by 1 x 10(-6) M naloxone did not change the potentiating SP-effect on vas deferens contractions. Blockade of the prostaglandin (PG) receptors by polyphloretin phosphate (PPP), 5 micrograms/ml, or of the PGs synthesis by indomethacin, 5 x 10(-6) M, resulted in a slight increase of the SP-potentiating effect. The present results suggest that specific presynaptic SP-receptors (excitatory or inhibitory) play a major role in the mechanism of the potentiating action of substance P.
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PMID:Smooth-muscle effects of substance P. 246 27

In this study, we have compared the effects of Substance P (SP) and an SP deprived of the N-terminal tripeptide, SP(4-11), on phosphoinositide metabolism by measuring phosphoinositide breakdown, inositol phosphate production and inositol incorporation into phosphoinositides. This work shows that SP and SP(4-11) have similar effects on phosphatidylinositol-4.5 bisphosphate (PIP2) metabolism. In fact, SP(4-11), like SP, induces a rapid PIP2 breakdown. On the contrary, SP and SP(4-11) have different effects on phosphatidylinositol (PI) metabolism since SP induces a decrease of radioactivity in PI, whereas SP(4-11) does not. Both peptides stimulate [3H]-inositol mono-, bis- and trisphosphate (respectively IP1, IP2, IP3) production in a time and dose-dependent manner. The kinetic of IP3 production is directly correlated with the one of PIP2 breakdown. The time course of IP1 production after SP(4-11) shows a time delay, while the one after SP does not. Since SP evokes an IP1 production without any delay and a large decrease of radioactivity in PI (which cannot account for the small amount measured in IP1 accumulation) we suggest that SP could activate a PI specific phospholipase C (leading to a PI breakdown) and a phospholipase D. These activations would require the complete structure of SP while the classical PIP2 specific phospholipase C activation (which induces PIP2 breakdown) would only require the carboxamide part of the peptide. So the complete structure of SP would be necessary to have a complete response (stimulation of PIP2 and PI metabolism).
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PMID:Importance of the presence of the N-terminal tripeptide of substance P for the stimulation of phosphatidylinositol metabolism in rat parotid gland: a possible activation of phospholipases C and D. 246 32

The present study was undertaken to study the ability of substance P (SP) to induce inositol phospholipid (IP) hydrolysis measured as inositol mono-phosphate (IP1) accumulation, in an in vivo blister model of neurogenic inflammation in the rat hind footpad. SP was found to induce IP1 accumulation in a concentration dependent manner. The use of SP analogues (SP5-11 and SP1-7) indicated that the response is mainly mediated by the C-terminal sequence of the peptide. The response was significantly reduced by the SP antagonist spantide, suggesting that the response is mostly due to activation of the SP receptor on small diameter vessels. Capsaicin pretreatment did not have an effect on the ability of SP to induce the response. Experiments with mepyramine suggest that the response is also partly mediated by SP induced histamine release from mast cells. This is the first study to provide direct evidence for phosphoinositide mediated SP effects in the skin.
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PMID:Substance P induced hydrolysis of inositol phospholipids in rat skin in an in vivo model of inflammation. 246 33

A high-performance liquid chromatographic method with fluorescence detection is described for the determination of substance P, one of the neuropeptides, in the hypothalamus tissue of rat brain. The detection is based on on-line post-column fluorescence derivatization selective for arginine-containing peptides. The endogenous substance P-like arginine-containing peptide extracted from the tissue and [D-Phe11]-neurotensin as an internal standard were separated from various interfering substances on a reversed-phase column (TSKgel ODS-120T) by gradient elution with acetonitrile-phosphate buffer (pH 2.3). The peptides in the eluate were then automatically converted into fluorescent derivatives for detection by reaction with benzoin. Arginine-containing fragments produced by the enzyme reaction of substance P in the chromatographic fraction with trypsin were also detected, for the identification of the endogenous substance P-like arginine-containing peptide. The method was sensitive enough to permit the quantitative determination of the peptide at a concentration as low as 580 fmol/mg of protein in the brain homogenate. The concentration values of the substance P-like arginine-containing peptide in the tissue were 9.45 +/- 1.50 pmol/mg of protein (six determinations).
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PMID:High-performance liquid chromatographic determination of substance P-like arginine-containing peptide in rat brain by on-line post-column fluorescence derivatization with benzoin. 247 17

A novel conditioned place preference (CPP) method is described. The behavioral testing apparatus is a circular open field consisting of 4 uniform quadrants that are equally preferred by the rats prior to drug treatment. In an illustrative experiment, rats received an i.p. injection of either morphine (10 mg/kg), substance P (50 micrograms/kg) or vehicle (phosphate-buffered 0.01 M acetic acid in saline) on 3 consecutive days and were placed into their assigned treatment quadrant. Four animals were simultaneously treated with the aid of barriers, which restricted each rat to its treatment quadrant. On the test for CPPs, when provided a choice between the 4 quadrants, rats treated with morphine and substance P exhibited preferences for the quadrant which had been paired with the drugs, illustrating the usefulness of this procedure for assessing the reinforcing properties of the two drugs. Gross locomotor activity was not influenced by either treatment. The advantages of this version of the CPP method over the conventional shuttle-box procedures are discussed.
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PMID:Conditioned place preference in the corral: a procedure for measuring reinforcing properties of drugs. 247 99

Autoinhibition of acetylcholine release by the coexisting peptide galanin in the septal afferents to the hippocampus of the rat was examined in tissue slices from the hippocampus. Galanin inhibits the evoked release of the coexisting neurotransmitter, acetylcholine, in the ventral hippocampus, providing an example of autoinhibition of release of a neurotransmitter by one of the coexisting neurotransmitters. The galanin mediated inhibition of the acetylcholine release is a complement to the well known strong cholinergic autoinhibition. The effects of the coexisting galanin and acetylcholine on several second messenger systems were also examined: acetylcholine acting at muscarinic receptors depresses cyclic adenosine 3',5'-monophosphate and stimulates elevation of cyclic guanosine 3',5'-monophosphate levels, whereas neither cyclic adenosine 3',5'-monophosphate nor cyclic guanosine 3',5'-monophosphate levels were affected by galanin (1 microM). Galanin however inhibited partly the muscarinic stimulation of phosphoinositide breakdown, suggesting that inositol phosphate(s) or diacylglycerol may act as second messenger(s) of the galanin action in the hippocampus. The effects of chronic changes in firing rate on the coexisting neurotransmitters in the rat ventral spinal cord containing serotonin, thyrotropin releasing hormone, substance P and substance K were examined. The tissue levels of the coexisting transmitters were studied in rats chronically treated with imipramine (14 days; 2 x 10 mumoles/kg/day) and zimelidine (14 days; 2 x 10 mumoles/kg/day). Upon treatment with zimelidine the tissue levels of the serotonin metabolite 5-hydroxyindoleacetic acid fall by 32% while thyrotropin releasing hormone levels seem to increase 35% and substance P/substance K levels also increase 48 and 72% respectively. Imipramine treatment resulted in similar although less pronounced changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic studies on functional aspects of coexistence. 248 72

The chemical nature of the spinal ganglionic neuron with peripheral processes projecting divergently to the somatic and visceral areas, has been identified by means of tri-labeling method of combining fluorescein tracing with immunocytochemistry. 10 rats were used. First, 2 microliters of 2% fast blue(FB) were injected into the left coeliac ganglion. Two days later, 2% nuclear yellow (NY) was injected into left 9-11 intercostal nerves, 1 microliter for each. On the 4th day, the animal was perfused with 10% formalin in 0.1 mol phosphate buffer. The left T9-11 spinal ganglia were removed and cut into sections by cryostat. The sections were observed under fluorescence microscope and photographed. The results showed that there were three kinds of neurons in the spinal ganglia: 1) single FB labeled cells with blue fluorescent cytoplasm accounted for 38.8% of total cells; 2) single NY labeled cells with yellow fluorescent nuclei accounted for 52.7%; 3) FB and NY double-labeled cells, mostly small or medium in size, accounted for 8.5%. Then, the sections containing double-labeled cells were further processed by substance P-demonstrating PAP immunocytochemical staining. The photographs with immunostaining and fluorescein labelings in the same section were compared. We found that the labeling ratio of SP/NY was 1.4%, SP/FB was 7%, and SP/NY + FB was 28.8%. The present study detected not only the convergence of somato-visceral sensation in the spinal ganglia but also the chemical nature of these neurons containing substance P (SP) for the first time. In addition, these results may provide a morphological basis for the mechanisms of referred pain and somato-visceral reflection.
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PMID:The somato-visceral divergent projections of peripheral processes of substance P-containing spinal ganglionic neurons--tri-labeling study of combining fluorescein tracing with immunocytochemistry. 248 59


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