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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However, forskolin (less than 1 microM) did not alter the contraction induced by substance P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP (1 microM)-induced contractions. 5. In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 microM). 6. These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.
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PMID:The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea-pig bronchi. 137 40

The effect of four different neuropeptides and norepinephrine (NE) on cyclic AMP formation in four different osteoblastic cell lines and in isolated neonatal mouse calvarial bone cells has been examined. In the rat osteosarcoma cell line UMR-106-01, vasoactive intestinal polypeptide (VIP, 0.001-1 microM), calcitonin gene-related peptide (CGRP, 0.3-30 nM), and NE (0.1-300 microM), but not neuropeptide Y (NPY, 0.001-1 microM) or substance P (SP, 0.1-10 microM), caused a dose-dependent stimulation of cyclic AMP formation. The stimulatory effects were synergistically potentiated by forskolin (0.1-3 microM). The effects of NE and VIP were time dependent, with an optimal effect seen at 5 minutes. The amount of cyclic AMP accumulated in cells stimulated with NE and VIP was in the same range. The amplitude of the cyclic AMP response induced by CGRP was smaller than that caused by VIP and NE. In the human osteosarcoma cell line Saos-2, NE (0.1 microM) and VIP (0.3 microM) stimulated cyclic AMP formation, and the effect was synergistically potentiated by forskolin. In the absence of forskolin, no effect of CGRP (30 nM) could be seen in the Saos-2 cells, but in the presence of forskolin (3 microM) a stimulatory effect was observed. SP and NPY did not change basal cyclic AMP levels in Saos-2 cells. In the osteoblastic osteosarcoma cell line of rat, ROS 17/2.8, NE (0.1 microM) caused a significant stimulatory action on cyclic AMP formation that was synergistically potentiated by forskolin (3 microM), VIP, CGRP, and SP did not affect the cellular content of cyclic AMP in ROS 17/2.8.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroendocrine regulation of cyclic AMP formation in osteoblastic cell lines (UMR-106-01, ROS 17/2.8, MC3T3-E1, and Saos-2) and primary bone cells. 138 76

The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1-7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were tested by combined single-unit extracellular recordings/microiontophoresis. While SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn nociceptive neurons. NMDA responses were transiently decreased (by an average of 36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by 76% at maximum). In contrast, AMP responses were only increased by SP-(1-7) (by 81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel mechanism by which SP and EAAs interact to modulate pain transmission.
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PMID:Modulation of N-methyl-D-aspartate and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a N-terminal fragment of substance P. 138 65

The aim of the present in vitro study was to provide information on the pharmacologic properties of the muscularis mucosae in three regions of the rabbit colon. Proximal muscularis mucosae exhibited spontaneous contractions whose frequency was independent of endogenous acetylcholine. In the mid and distal colon, spontaneous contractile frequencies were depressed by atropine and enhanced by eserine. Muscularis mucosae from all regions responded to acetylcholine, ADP, AMP, ATP, bradykinin, histamine, methoxamine, substance P, vasoactive intestinal polypeptide but not cholecystokinin octapeptide or gamma-aminobutyric acid. Low concentrations of norepinephrine caused propranolol-sensitive relaxations of proximal colonic muscularis mucosae whereas high concentrations evoked phentolamine-sensitive contractions. In the mid and distal colon, norepinephrine caused relaxations which were poorly antagonized by propranolol. Proximal colonic muscularis mucosae responded to electrical stimulation with an atropine- and tetrodotoxin-sensitive "on contraction." Responses from the mid and distal colon were tetrodotoxin-sensitive and consisted of an atropine-sensitive "duration contraction" followed by a propranolol-insensitive "off relaxation" which was not mediated by prostaglandin synthesis, a purine, or vasoactive intestinal polypeptide. These data suggest that the rabbit colonic muscularis mucosae possesses alpha-1 adrenoceptors, histamine H1, muscarinic, P2 purinoceptors and beta adrenoceptors. However, their relative importance and the nature of the intrinsic innervation suggests considerable specialization of this muscle layer in different regions of the rabbit colon.
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PMID:Pharmacologic characterization of the muscularis mucosae in three regions of the rabbit colon. 160 78

Isolated human gastroepiploic vein tributaries responded to dopamine only with contractions, whereas the gastroepiploic artery branches in the same region of the omentum responded with relaxations. Treatment with phentolamine converted the vein contraction to a relaxation, which was not influenced by propranolol but was abolished by droperidol. The relaxation was converted to a contraction by SCH23390 but unaffected by domperidone. Endothelium denudation abolished the relaxation caused by substance P but did not significantly alter the dopamine-induced relaxation. Dopamine increased the cyclic AMP content in the human veins. Monkey mesenteric, renal and portal veins and vena cava contracted in response to dopamine. Treatment with phentolamine converted the contraction to a slight relaxation in the mesenteric and renal veins; however, even in the presence of high concentrations of the alpha adrenoceptor antagonist, no relaxation was induced in the portal vein and vena cava partially contracted with prostaglandin F2 alpha. It is concluded that gastroepiploic veins and arteries in the human omentum respond quite differently to dopamine; the alpha adrenoceptor-mediated contraction predominates over the relaxation mediated via dopamine D1 receptor subtype in the veins, and vice versa in the arteries. Dopamine relaxes the human vein, possibly as a result of increased production of intracellular cyclic AMP by stimulation of D1 receptors. The predominant action of dopamine on alpha adrenoceptors may contribute to increasing venous return and cardiac output.
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PMID:Responses to dopamine of isolated human and monkey veins compared with those of the arteries. 164 95

Neurokinins are a family of neuropeptides with widespread distribution mediating a broad spectrum of physiological actions through three distinct receptor subtypes: NK-1, NK-2, and NK-3. We investigated some of the second messenger and cellular processes under control by the recombinant bovine NK-2 receptor stably expressed in Chinese hamster ovary cells. In this system the NK-2 receptor displays its expected pharmacological characteristics, and the physiological agonist neurokinin A stimulates several cellular responses. These include 1) transient inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization, 2) increased out put of arachidonic acid and prostaglandin E2 (PGE2), 3) enhanced cyclic AMP (cAMP) generation, 4) increased de novo DNA synthesis, and 5) an induction of the "immediate early" genes c-fos and c-jun. Although NK-2 receptor-mediated IP3 formation involves activation of a pertussis toxin-insensitive G-protein, increased cAMP production is largely a secondary response and can be at least partially attributed to autocrine stimulation by endogenously generated eicosanoids, particularly PGE2. This is the first demonstration that a single recombinant neurokinin receptor subtype can regulate, either directly or indirectly, multiple signal transduction pathways and suggests several potential important mediators of neurokinin actions under physiological conditions.
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PMID:Recombinant bovine neurokinin-2 receptor stably expressed in Chinese hamster ovary cells couples to multiple signal transduction pathways. 166 1

Substance P was incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the peptide on D-1 receptor coupled adenylate cyclase in vitro. Substance P did not influence basal adenylate cyclase activity or the stimulation of the enzyme by dopamine. No influence of substance P was seen on the effects of calcium and magnesium chloride as a cofactor of adenylate cyclase. Also the inhibition of adenylate cyclase activity by the dopamine antagonist fluphenazine was not influenced by substance P. However, substance P was able to enhance cyclic AMP formation in the presence of guanosine-imidodiphosphate (Gpp(NH)p), whereas the stimulatory effect of guanosine-triphosphate (GTP) was inhibited by substance P. In our study we suggest that substance P interacts with the guanine nucleotide regulatory subunit without directly affecting D-1 dopamine receptors in the caudate-putamen of the rat.
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PMID:Guanine nucleotides regulate the effect of substance P on striatal adenylate cyclase of the rat. 169 2

Desensitization occurs when the response to a neurotransmitter receptor agonist wanes in the continued presence of agonist. In amphibian sympathetic neurons, both muscarinic and peptidergic receptor agonists inhibit a K+ current, the M-current (IM), and this inhibition desensitizes. We have studied the desensitization to substance P (SP) by whole-cell recordings from dissociated sympathetic neurons from bullfrogs. When ATP in the recording pipette was replaced with AMP-PNP, SP still inhibited IM, but no desensitization was observed, indicating that ATP hydrolysis is required for desensitization. Desensitization inhibitors of beta-adrenergic receptors did not block desensitization to SP. When a low dose of muscarine sufficient to inhibit IM, but not to elicit desensitization, was applied simultaneously with a desensitizing dose of SP, IM remained depressed and did not desensitize. Thus, there may be separate systems controlling desensitization for different agonists, or the enzyme(s) involved is "compartmentalized."
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PMID:Desensitization of the inhibition of the M-current in sympathetic neurons: effects of ATP analogs, polyanions, and multiple agonist applications. 169 Oct 6

The discovery of peptides in the splanchnic nerve and adrenal gland, and their co-existence with conventional neurotransmitters raises questions about their possible functional roles in catecholamine (CA) secretion and gene transcription in the adrenal gland. Short-term, stress-induced CA secretion is regulated biphasically by substance P (SP) which inhibits acetylcholine (ACh) action at SP greater than 10(-6) M and facilitates CA secretion in response to metabolic and physical stressors, ACh or electrical stimulation at SP less than 10(-6) M. Long-term, gene transcription of phenylethanolamine-N-methyltransferase (PNMT) is exerted by glucocorticoids, and gene transcription of Proenkephalin-A by agents such as histamine, angiotensin II and VIP that increase cyclic AMP (cAMP). The final products of these two genes, adrenaline and Met-enkephalin and congeners, are co-stored in chromaffin granules of adrenaline cells but gene expression of these products is clearly under differential control.
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PMID:Peptide regulation of adrenal medullary function. 169 30

Two novel neuromedin C analogs [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, were synthesized by rapid solid phase methods and examined for their abilities to inhibit neuromedin C-stimulated amylase release by isolated rat pancreatic acini. Both analogs significantly inhibited maximally stimulated amylase release by neuromedin C in a dose-dependent manner with maximal inhibition seen at concentrations of 100 and 300 microM of [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C and [Leu9-psi-CH2NH-Leu10]neuromedin C, respectively. The IC50 (concentration required to half-maximally inhibit neuromedin C-stimulated amylase release) was 1.5 microM for [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C compared to a 13.4 microM IC50 for [Leu9-psi-CH2NH-Leu10]neuromedin C. The [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C analog produced a parallel rightward shift in the neuromedin C dose-response curve and Schild plots of the inhibition data gave a slope of 0.969 +/- 0.121 and a pA2 (apparent affinity for the acinar cell receptor in terms of neuromedin C receptor-stimulated amylase release) of 100 nM. While [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C significantly inhibited both neuromedin B- and gastrin releasing peptide-stimulated amylase release, the analog did not inhibit amylase release in response to either cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, carbamylcholine, the Ca2+ ionophore A23187, forskolin, or 8-bromo-cyclic AMP. The results demonstrate that [D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C is a potent, specific, and competitive antagonist for neuromedin C and peptides of the gastrin releasing peptide family and may serve as a useful molecule for exploring the physiological role of these peptides.
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PMID:[D-Ala1, Leu9-psi-CH2NH-Leu10]neuromedin C antagonizes neuromedin C-stimulated amylase release by acini isolated from the rat pancreas. 169 79


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