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)

In this work, we have studied the effects and the possible cellular mechanism of Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele crested newt, Triturus carnifex. Adrenals were in vitro superfused with SP, prostaglandin E2 (PGE2), nitric oxide (NO) donor, cyclic GMP (cGMP) analogue, and inhibitors of phospholipase A1, phospholipase A2 (PLA2), phospholipase C, adenylate cyclase (AC), cyclooxygenase (COX), NO synthase (NOS), and soluble guanylate cyclase (sGC). PGE2, corticosterone, and aldosterone release and NOS activity were determined. SP, PGE2, NO donor, and cGMP analogue increased corticosterone and aldosterone; SP and PGE2 increased NOS, and SP increased PGE2. PLA2, AC, COX, NOS, and sGC inhibitors counteracted SP and PGE2 effects, except for PLA2, which did not affect PGE2. These results suggest that SP exhibits a stimulatory role on the corticosteroidogenesis of T. carnifex adrenal gland. In particular SP enhances PLA2 activity, increasing PGE2; this prostaglandin affects AC, which, in turn, enhances NO, and the latter therefore affects sGC, with the consequent corticosteroidogenesis increase.
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PMID:Cellular mechanism of substance P in the regulation of corticosteroid secretion by newt adrenal gland. 914 46

Following electroconvulsive treatment (ECT) of rabbits, preprotachykinin-A (PPT-A) mRNA was detected by Southern blot analysis of polymerase chain reaction (PCR)-amplified products in the cerebrospinal fluid (CSF) and aqueous humor of the eye. In contrast, no PPT-A mRNA could be detected in samples from untreated animals. In addition, several neuropeptides (substance P, neuropeptide Y, cholecystokinin, calcitonin gene-related peptide and pituitary adenylate cyclase activating peptide) were released into the CSF (and aqueous humor) following ECT. The results suggest that PPT-A mRNA was released together with neuropeptides into the CSF and aqueous humor in response to ECT. Indeed, previous studies have suggested that neurons can release neuropeptide mRNAs and that neurons are capable of taking up and expressing foreign mRNA. If neuropeptide mRNA can be taken up and utilized by another neuronal population, it might explain instances when neurons display 'phenotypic switch', i.e. the transient expression of novel neuropeptides.
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PMID:Electroconvulsive treatment evokes release of preprotachykinin-A mRNA into the cerebrospinal fluid and ocular aqueous humor of rabbits. 917 89

We investigated the effect of neuropeptides, which are vasoactive intestinal polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA), somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine-enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had no effect. Especially, VIP showed the most effective in inhibiting tumor invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was also observed in cell migration to fibronectin. VIP had no effect on the growth of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. These results indicate that VIP, among the neuropeptides used, could inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial suppression of their motility, and the reduction was associated with an intracellular cAMP-mediated pathway.
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PMID:Differential effect of intestinal neuropeptides on invasion and migration of colon carcinoma cells in vitro. 1837 31

Pituitary adenylate cyclase activating polypeptide (PACAP), a member of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family, is known to be a powerful stimulator of adenylate cyclase. Recently, PACAP has been shown to stimulate cAMP in osteoblast-like cells and mouse calvarian bones. In the present study, PACAP immunoreactivity (IR) was demonstrated in cartilage canals from newborn and 3-4-week-old pigs. In tissues from the femoral head and the patella with and without ossification centres, PACAP-IR nerve fibres were found in the cartilage canals innervating blood vessels. The pattern of distribution was not dependent on age or the occurrence of an ossification centre. Co-localization studies showed a high degree of co-localization with calcitonin gene-related peptide (CGRP) and substance P (SP) but little co-localization with VIP. Our findings support earlier findings of CGRP, SP and VIP in bone tissue and add PACAP to the group of neuropeptides with a sensory and/or modulatory function in bone tissue.
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PMID:Immunocytochemical demonstration of pituitary adenylate cyclase activating polypeptide (PACAP) in the porcine epiphyseal cartilage canals. 917 66

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 and Val19 of the natural peptide were replaced by phenylalanyl and tyrosyl residues: [Phe13, Tyr19]-MCH. The peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and polyhipe PA 500 and PEG-PS resins. The linear MCH peptides with either acetamidomethyl-protected or free cysteinyl residues were purified to homogeneity and cyclized by iodine oxidation, yielding the final product with the correct molecular weight of 2434.61. Radioiodination of the C-terminal tyrosine was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and by high-pressure liquid chromatography. The resulting [125I]-[Phe13, Tyr19]-MCH tracer was the first radiolabelled MCH peptide suitable for radioreceptor assay: saturation binding analysis using mouse G4F-7 melanoma cells demonstrated the presence of 1090 MCH receptors per cell. The dissociation constant (KD) was 1.18 x 10(-10) M, indicating high-affinity MCH receptors on these cells. MCH receptors were also found in other cell lines such as mouse B16-F1 and G4F and human RE melanoma cells as well as in PC12 and COS-7 cells. Competition binding analyses with a number of other peptides such as alpha-MSH, neuropeptide Y, substance P and pituitary adenylate cyclase activating peptide, demonstrated that the binding to the MCH receptor is specific. Atrial natriuretic factor was found to be a weak competitor of MCH, indicating topological similarities between MCH and ANF when interacting with MCH receptors.
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PMID:Synthesis and iodination of human (phenylalanine 13, tyrosine 19) melanin-concentrating hormone for radioreceptor assay. 922 84

The aims of this study were to determine the effect and mechanism of action of pituitary adenylate cyclase-activating peptide (PACAP) on gallbladder muscle. Guinea pig gallbladder muscle strips were studied isometrically. In noncontracted muscle strips, PACAP-27 and PACAP-38 caused dose-dependent contractions, whereas vasoactive intestinal peptide (VIP) caused dose-dependent relaxation. PACAP-27 contractions were resistant to tetrodotoxin, atropine, and the substance P receptor antagonist [D-Arg1,D-Trp7,9,Leu11]substance P (Spantide) but were inhibited by the selective PACAP receptor antagonist PACAP-(6-38) and slightly increased with the VIP receptor antagonist [4-chloro-D-Phe6,Leu17]VIP. In cholecystokinin-precontracted muscle strips, both VIP and PACAP caused relaxations. This relaxant effect of PACAP-27 was inhibited by PACAP-(6-38) and [4-chloro-D-Phe6,Leu17]VIP, but not by tetrodotoxin. These studies suggest that PACAP has dual excitatory and inhibitory effects on guinea pig gallbladder muscle. The contractile effect of PACAP is a direct action on muscle through PACAP-preferring receptors. The relaxant effect of PACAP is seen in precontracted muscle strips and mediated through VIP/ PACAP-preferring receptors.
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PMID:Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP/PACAP-preferring receptors. 922 79

Four tachykinin-related peptides, locustatachykinin 1-4 (LomTK 1-4) are distributed in interneurons throughout the central nervous system of the locust Locusta migratoria and may have important roles as neurotransmitters or neuromodulators. In search of the central actions of LomTKs, we analyzed the response of the efferent dorsal unpaired median (DUM) neurons in the locust metathoracic ganglion. Immunocytochemistry, using an antiserum against LomTK 1, combined with intracellular filling of efferent DUM neurons with Lucifer yellow, revealed that LomTK-immunoreactive fibers are in close proximity to dendritic arborizations of the DUM neurons. Hence, LomTKs may act on DUM neurons by releasing locally in the metathoracic ganglion. Intracellular recordings were made from somata of DUM neurons, and LomTKs were either bath-applied to an isolated metathoracic ganglion or pressure-ejected onto the DUM neuron soma. LomTK 1 at concentrations of 0.1 mM-0.1 microM caused a relatively slow, reversible depolarization with a subsequent increase in the frequency of action potential firing. Amino-terminally truncated forms of LomTK 1 were applied to DUM neurons. The heptapeptide [3-9]-LomTK 1 had a substantially reduced activity, and bioactivity was lost after further truncation. Spantide 1, an antagonist of mammalian tachykinin receptors, reversibly blocked the effect of LomTK 1. The effect of LomTK 1 was clearly reduced in the presence of GDP-beta-S, a stable analog of GDP that inactivates G-proteins. The action of LomTK 1 was potentiated by both IBMX and theophylline, two cyclic AMP (cAMP) phosphodiesterase inhibitors. The action of LomTK 1 was mimicked by pressure-ejecting 8-bromo-cAMP, a membrane permeable analog of cAMP, and by forskolin, an adenylate cyclase activator. Furthermore, cAMPS, a blocker of protein kinase A activity, reduced the effect of LomTK 1. These findings indicate that cAMP is involved in mediating DUM neuron depolarization.
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PMID:Peptidergic activation of locust dorsal unpaired median neurons: depolarization induced by locustatachykinins may be mediated by cyclic AMP. 929 67

The regulation of Ca2+ mobilization in the human submandibular duct cell line A253 was investigated by monitoring cytosolic free Ca2+ concentrations ([Ca2+]i) using the Ca(2+)-sensitive fluorescent indicator fura-2 and by measuring inositol 1,4,5-triphosphate (IP3) formation. An increase in [Ca2+]i was elicited by ATP, isoproterenol (IPR), or vasoactive intestinal polypeptide (VIP), but not by acetylcholine, norepinephrine, or substance P, suggesting that Ca2+ mobilization is regulated by P2-purinergic, beta 2-adrenergic, and VIP receptors. 1,4,5-IP3 formation was significantly increased by ATP but not by the other agonists. Exposure of the cells to a membrane permeable cAMP analog, dibutyryl-cAMP, or to the adenylate cyclase activator forskolin induced a smaller increase in [Ca2+]i, indicating that the IPR-induced Ca2+ release is not mediated by cyclic AMP. Inhibition of the endoplasmic Ca(2+)-ATPase with thapsigargin (TG) in Ca(2+)-free medium induced a 207% increase in [Ca2+]i, and a subsequent exposure to ATP caused a further increase in [Ca2+]i of 104%. Similarly, TG exposure after ATP induced a further Ca2+ release, suggesting that the TG-sensitive store and the IP3-sensitive store do not overlap. Similar results were observed by sequential exposure to TG and IPR or to ATP and IPR. Ca2+ influx across the plasma membrane was enhanced after ATP or TG, but not after IPR. Our findings show a unique pattern of Ca2+ mobilization in the A253 cell line: (i) Ca2+ mobilization is regulated by P2-purinergic, beta 2-adrenergic, and VIP receptors; (ii) Ca2+ release is mediated by 1,4,5-IP3 and probably by an unknown mediator; (iii) TG, P2-, and beta 2-agonists discharge separate Ca2+ stores; and (iv) ATP and TG, but not IPR, regulate Ca2+ influx.
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PMID:Characterization of Ca2+ mobilization in the human submandibular duct cell line A253. 931 20

Unlike its effects on the rest of the GI tract, the effects of pituitary adenylate cyclase-activating peptide (PACAP) on the internal anal sphincter (IAS) are not known. We examined the actions of PACAP-38 (here PACAP) and PACAP-27 on the basal IAS tone of circular smooth muscle strips before and after the administration of different neurohumoral antagonists. PACAP caused a concentration-dependent fall in the basal tone of the IAS. Interestingly, however, at higher concentrations, PACAP caused a biphasic response: an initial contraction followed by a relaxation. Both the contractile and the relaxant responses were insensitive to atropine, guanethidine, apamin or tetrodotoxin. Both the contractile and the relaxant effects were inhibited by PACAP 6-38 (a selective antagonist of PACAP), vasoactive intestinal polypeptide 10-28 (a vasoactive intestinal polypeptide antagonist) and PACAP tachyphylaxis. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine attenuated the inhibitory but not the excitatory effect of PACAP. Conversely, the contractile but not the relaxant effect of PACAP on the IAS was nearly obliterated by the substance P antagonist spantide. The N-type Ca++-channel blocker omega-conotoxin caused significant suppression of both the contractile and the inhibitory actions of PACAP. We conclude that in the IAS, PACAP has a dual effect: a contraction followed by a relaxation. The contraction of IAS by PACAP is speculated to occur via the activation of PACAP receptor at the substance P-containing nerve terminals. PACAP-induced IAS relaxation, on the other hand, appears to be mediated in large part by its direct action at the smooth muscle cells and in part by its action at the nerve terminals of the myenteric inhibitory neurons.
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PMID:Excitatory and inhibitory actions of pituitary adenylate cyclase-activating peptide (PACAP) in the internal anal sphincter smooth muscle: sites of actions. 935 91

The effects of pituitary adenylate cyclase activating peptide (PACAP) 38, PACAP 27 and vasoactive intestinal peptide (VIP) on plasma extravasation were investigated in vivo in rat skin. PACAP 38, PACAP 27 and VIP, caused concentration-dependent extravasation in rat skin. The order of potency was PACAP 38 > PACAP 27 = VIP, whereas the order of maximal induced extravasation was PACAP 38 = PACAP 27 > VIP, suggesting that PACAP 38 might be the most powerful inducer of plasma extravasation of the three tested members of the secretin-glucagon-VIP family. Substance P (SP) was about 5 times more potent than PACAP 38 and 15 times more potent than PACAP 27. These data indicate that PACAP 38 induced plasma extravasation in concentrations roughly equimolar to SP. Pyrilamine (H1 receptor antagonist) reduced the PACAP 38-induced plasma extravasation more than 50%; cimetidine (H2 receptor antagonist) was without effect. To investigate whether a cAMP-mediated process is involved in the induction of plasma extravasation, the synthetic adenosine 3',5'-cyclic monophosphate (cAMP), dibutyryl adenosine cyclic monophosphate (DBcAMP) and the cAMP-inducing drug, salbutamol, were each injected in the skin; neither of these drugs caused extravasation. We conclude that PACAP 38 and PACAP 27 cause potent plasma extravasation which, at least in part, involves histamine release.
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PMID:PACAP-induced plasma extravasation in rat skin. 941 88


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