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 tachykinins (TKs) are a family of small peptides which share the common C-terminal sequence Phe-X-Gly-Leu-MetNH2. Three peptides of this family, substance P, neurokinin A and neurokinin B, have an established role as neurotransmitters in mammals. 2. Three receptors for TKs have been cloned: they are G-protein coupled receptors with seven putative transmembrane spanning segments and have been termed NK1 (substance P-preferring), NK2 (neurokinin A-preferring) and NK3 (neurokinin B-preferring). 3. Synthetic agonists are available to selectively stimulate only one receptor, while natural TKs can act as full agonist at each one of the three receptors, albeit at different concentrations. 4. A number of potent and selective antagonists, both peptide and nonpeptide in nature, have recently been developed. 5. The introduction of these ligands has revealed an unforeseen pharmacological heterogeneity of NK1, NK2 and NK3 receptors which appears largely, if not exclusively, linked to the existence of species homologues of the three receptors.
Gen Pharmacol 1995 Sep
PMID:The mammalian tachykinin receptors. 755 66

1. We investigated the ability of ruthenium red, an inorganic dye with capsaicin antagonist properties, to inhibit capsaicin-induced plasma extravasation in the rat trachea. 2. The amount of plasma extravasation produced by intravenous capsaicin was reduced dose-dependently by i.v. ruthenium red. Complete inhibition was achieved with a dose of 5 mumol/kg. 3. The inhibitory effect of ruthenium red persisted for at least 16 hr after its administration, but was not present 24 hr later. 4. Ruthenium red did not reduce the amount of plasma extravasation produced by electrical stimulation of the vagus nerve, nor the amount produced by intravenous substance P or platelet-activating factor. 5. Prior exposure to a high dose of capsaicin reduced the amount of plasma extravasation produced by a second capsaicin exposure 48 hr later. However, giving ruthenium red 30 min before the initial capsaicin exposure largely prevented this loss of sensory nerve function. 6. We conclude that systemic administration of ruthenium red produces long-lasting, selective, and reversible inhibition of capsaicin-induced plasma extravasation in the rat trachea. Moreover, ruthenium red attenuates the long-term, desensitizing effect of capsaicin on sensory nerves.
Gen Pharmacol 1995 Mar
PMID:Characterization of ruthenium red as an inhibitor of neurogenic inflammation in the rat trachea. 759 82

1. Gastric blood flow and motor responses to greater splanchnic nerve stimulation and intra-arterial injection of tachykinins were studied in anaesthetized dogs. 2. Splanchnic nerve stimulation (40 V, 10 Hz) with pulse durations of 0.05 and 1 msec caused a gastric relaxation and contraction, respectively. Both types of stimulation produced a decrease followed by an increase in blood flow. The responses to stimulation with a pulse duration of 0.05 msec were inhibited by hexamethonium. 3. After treatment with hexamethonium, stimulation with 1 msec caused frequency-dependent gastric contraction and vasodilation. Both responses had two components, sensitive and resistant to atropine. 4. Intra-arterial injection of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY) or eledoisin (ELE) elicited dose-dependent gastric contraction and vasodilation. The order of potency for contraction was SP = PHY = ELE = NKA >> NKB and that for vasodilation was SP = PHY > ELE > NKA > NKB. 5. Atropine partly inhibited the tachykinin-induced gastric contraction but not gastric vasodilation. Spantide partly inhibited the atropine-resistant vasodilation but not contraction in response to splanchnic nerve stimulation and SP. 6. It is concluded that splanchnic nerve stimulation produced cholinergic and SPergic vasodilation after ganglionic blockade in the dog stomach.
Gen Pharmacol 1993 Mar
PMID:Gastric vasodilator and motor responses to splanchnic stimulation and tachykinins in the dog. 768 99

1. Functional changes in the urinary bladder obtained from streptozotocin-induced diabetic rats were investigated by determining the responsiveness of bladder strips to capsaicin or substance P (SP). 2. Contractile responses of detrusor strips of the urinary bladder in response to capsaicin were almost abolished in both diabetic rats and capsaicin-pretreated rats. 3. Maximal contractions of diabetic detrusor strips induced by SP were significantly increased when compared to age-matched controls. 4. In contrast to the contractile responses to SP, the density of SP receptors was significantly decreased in diabetic rats. 5. The increased contractile responses to SP were markedly decreased by treatment with indomethacin, OKY-046 or quinacrine, but not with nordihydroguaiaretic acid. 6. Contractile responses of detrusor strips to prostaglandin F2 alpha and E2 were unchanged in the diabetic state. 7. These results suggest that the increased contractile responses of detrusor strips of the bladder to SP in the diabetic state are due to increased synthesis of prostaglandins and/or thromboxane A2 via the increased activity of phospholipase A2 on the smooth muscle of the diabetic bladder.
Gen Pharmacol 1993 May
PMID:Changes in contractile responses of the urinary bladder to substance P in streptozotocin-induced diabetic rats. 768 96

The intrathecal (i.th., T8-10) administration in conscious rats of the 5-hydroxytryptamine (5-HT)1A agonist 8-OH-DPAT (10 nmol), and to a lesser extent the 5-HT1B agonist CGS 12066B (6 nmol), resulted in a blood pressure reduction and a bradycardia. These responses were prevented by the i.th. pretreatment with substance P (SP) (6.5 nmol) and enhanced following pretreatment with the non-peptide SP antagonist CP-96,345 (10 nmol). The partial 5-HT1A agonist 8-MeO-CLEPAT (10 nmol) had by itself small cardiovascular effects. Following the pretreatment with SP, 8-MeO-CLEPAT caused a pressor response and a tachycardia whereas the opposite effects were observed following pretreatment with the SP antagonist. These results support the notion of a functional interaction between serotonergic and SP mechanisms at the level of the preganglionic sympathetic nerves in the spinal cord.
J Neural Transm Gen Sect 1993
PMID:Cardiovascular effects of intrathecal administration of agents active at 5-hydroxytryptamine1-receptors in the rat: modulation by substance P and a substance P antagonist. 769 86

1. The depressor responses to i.a. and i.v. injection of capsaicin (CAP) were blocked following intrathecal (i.t.) perfusion of [D-Pro2, D-Trp7,9] substance P, a specific substance P antagonist. This confirmed that the CAP-elicited depressor reflex is mediated by substance P-containing afferent fibres. 2. The regulatory roles of spinal adenosine in the CAP-evoked substance P release and the possible involvement of adenosine A2 receptors were analyzed by analyzing the changes in cardiovascular responses to i.a. and i.v. injection of CAP after various pretreatments with adenosine agonists and antagonists, administered subcutaneously or intrathecally.
Gen Pharmacol 1993 Jul
PMID:Spinal adenosine modulates capsaicin-induced depressor reflex: involvement of adenosine A2 receptor. 769 43

1. An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the substance P (SP)/neurokinin-1 (SP/NK1) receptor was constructed and added to cultures of human astrocytoma U-87 MG cells in vitro and rats in vivo. 2. Antisense oligodeoxynucleotide at a concentration of 30 microM progressively reduced the specific binding [3H][Sar9, Met(O2)11]-SP, selective SP/NK1 receptor agonist, in the U-87 MG astrocytoma cells by approx. 31% on the second day after treatment (control: 26.1 +/- 2.4 fmol/mg protein vs antisense oligodeoxynucleotide: 18.0 +/- 1.4 fmol/mg protein, P < 0.001). 3. Treatment with 30 microM antisense oligodeoxynucleotide for 2 days inhibited the SP/MK1 receptor-induced influx of 45Ca2+ into the U-87 MG cells by approx. 35%. 4. When the same antisense oligodeoxynucleotides were encapsulated in liposomes and injected into the lateral cerebral ventricle of rats, functional SP receptor was blocked.
Gen Pharmacol 1994 Oct
PMID:Modulation of substance P/neurokinin-1 receptor in human astrocytoma cells by antisense oligodeoxynucleotides. 787 35

1. This review discusses factors contributing to acute joint inflammation, particularly sensory neuropeptides. 2. Mediators known to contribute importantly to the inflammatory process include cytokines, eicosanoids, complement and the kinin systems, histamine and 5-hydroxytryptamine and sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). 3. The pro-inflammatory neurokinins, SP and CGRP, are present in nerves innervating joints and could significantly contribute to the increased vascular permeability and hyperaemia occurring in acute arthritis. 4. Although perhaps contributing to the pathogenesis of chronic inflammatory joint disease, there is little evidence for involvement of the sympathetic nervous system in acute models of inflammation.
Gen Pharmacol 1994 Nov
PMID:Acute joint inflammation--mechanisms and mediators. 789 38

1. Experiments were designed to study the effects of ageing on muscarine and NK2 receptor mechanisms in the three different regions of rabbit airway. 2. The pD2 value of acetylcholine changed with age in three different regions while that of carbamylcholine, which is resistant to acetylcholinesterase, did not. 3. The pD2 values of neurokinin A and the activity of protease, a degradative enzyme, changed with age. However, by the pretreatment with phosphoramidon, a protease inhibitor, the regional difference and age related change of the pD2 value of neurokinin A disappeared. 4. In conclusion, the observations about age related changes and regional differences of pD2 value of acetylcholine and neurokinin A were due to the difference of their degradative enzyme activities.
Gen Pharmacol 1994 Jul
PMID:Effects of ageing on regional differences in the contractile responses to acetylcholine and neurokinin A in rabbit airway. 795 29

This work examines the connectivity of the olfactory bulb in the gynmotiform fish Apteronotus leptorhynchus. Wheat germ agglutinin conjugated horseradish peroxidase was iontophoresed in different areas and depths of the bulb in order to define its efferent and afferent connections. The olfactory bulb projects bilaterally via the medial (medial and centromedial fascicles) and lateral olfactory (lateral and centrolateral fascicles) tracts. The nervus terminalis courses through the ventromedial aspect of the bulb to terminate in parts of the medial subpallium and hypothalamus. Its telencephalic component could be identified by a nonpreadsorbable substance P-like immunoreactivity. Fibers within the medial olfactory tract form four telencephalic terminal fields: peduncular, medial, intermediate and posterior fields. The diencephalic terminal fields in the habenula, preoptic, and hypothalamic areas appear to correspond to some of the nervus terminalis fibers (von Bartheld and Meyer [1986] Cell Tissue Res. 245:143-158, Krishna et al. [1992] Gen. Comp. Endocrinol. 85:111-117), and to axons of telencephalic bulbopetal cells of area dorsalis posterior. The terminal fields of the medial olfactory tract and nervus terminalis partially overlap in the ventral telencephalic areas partes ventralis, supracommissuralis, and rostral preoptic region. The lateral olfactory tract forms a lateral terminal field and contributes to the intermediate and posterior terminal fields. Olfactory fibers cross in the interbulbar, anterior, and habenular commissures and tuberal decussation. Consistent differences were noted between the medial and lateral olfactory bulb, with respect to their cytoarchitectonics, immunohistochemistry, and connections. In addition to the olfactory nerve, bulbar afferents are predominantly ipsilateral, with minor inputs originating from the contralateral bulb and telencephalic area dorsalis posterior, nucleus raphe centralis, and locus ceruleus.
 ...
PMID:Connections of the olfactory bulb in the gymnotiform fish, Apteronotus leptorhynchus. 822 32


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