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. Application of capsaicin solution onto the rat pharyngeal mucosa caused a well-reproducible increase in vascular permeability in the pharynx. 2. Capsaicin-induced pharyngeal inflammation was unaffected by a histamine H1 blocker and non-steroidal anti-inflammatory agents, whereas dexamethasone was effective in its inhibition. 3. FK224, a dual antagonist of tachykinin NK1 and NK2 receptors, and FK888, a selective antagonist of NK1 receptor, significantly inhibited capsaicin-induced plasma exudation in the pharynx. 4. In capsaicinized animals, the application of capsaicin solution in the pharyngeal mucosa did not induce pharyngitis. 5. These results suggest that the mechanism of the capsaicin-induced pharyngitis primarily involves tachykinins.
Gen Pharmacol 1998 Jan
PMID:A new pharyngitis model using capsaicin in rats. 945 90

1. The possible contribution of the nonadrenergic noncholinergic (NANC) transmitters nitric oxide (NO) and substance P (SP) to the contractility of guinea pig isolated ileum was studied by the responses of the longitudinal muscle to electrical field stimulation (0.8 msec, 40 V, 1-20 Hz, 20 sec) of the intrinsic nerves and by the presence and distribution of NADPH-diaphorase- and SP-positive nerve structures in the myenteric plexus. 2. The electrically elicited, tetrodotoxin (0.3 microM)-sensitive responses, in the presence of phentolamine (5 microM), propranol (5 microM), and atropine (3 microM) consisted of relaxation, followed by twitch and tonic contraction on which phasic contractions were superimposed. 3. NG-nitro-L-arginine (L-NNA; 0.1 mM or 0.5 mM), an inhibitor of NO synthesis abolished the relaxation. L-arginine (0.1 mM), a substrate for NO synthesis, but not D-arginine, restored it. L-NNA concentration dependently increased the twitch and tonic contractions. Sodium nitroprusside (1 microM or 10 (M), an exogenous donor of NO, was without effect on the electrically evoked responses. 4. AP 13.2 ACOH (AP; 0.1 microM or 10 microM), a blocker of SP receptors, frequency dependently inhibited or even prevented the twitch and tonic contractions. AP concentration-dependently increased the relaxation or reversed the responses to electrical stimulation into a deep relaxation. 5. The concentration-response curve for SP (1 nM-0.1 microM) was shifted to the right by AP, the EC50 values being 5.2 +/- 0.4 nM and 88.0 +/- 3.0 nM, respectively. The effects of SP were not altered by L-NNA (0.1 mM). 6. These findings, supported by morphological data about distribution of NADPH-diaphorase-positive nerve cell bodies and processes and SP-positive varicose fibers, suggest the contribution of NO and SP to NANC transmission. It appears that NO inhibits prejunctionally the SP transmission whereas SP counteracts the NO effect at the postjunctional level.
Gen Pharmacol 1998 Jul
PMID:Contribution of nitric oxide and substance P to nonadrenergic, noncholinergic transmission in the guinea pig ileum. 959 87

1. The effects of rat calcitonin gene-related peptide (rCGRP), rat calcitonin (rCT) and salmon calcitonin (sCT) on the substance P-mediated (SP-mediated) secretion of fluid from the rat submandibular gland were investigated. 2. Rat CGRP potentiated and prolonged the SP-mediated secretion of fluid from the rat submandibular gland in a dose-dependent manner. CGRP also enhanced methacholine- and phenylephrine-mediated secretion of fluid. 3. The potentiating effect of the combination of rCGRP and SP was somewhat reduced by pretreatment with spantide, human CGRP8-37 and atropine but not by pretreatment with phentolamine or with propranolol. 4. Salmon CT at a low dose mimicked the effect of rCGRP on the SP-mediated secretion of fluid, but its potency was lower than that of rCGRP. However, rCT had no effect on the SP-mediated secretion of fluid. 5. These results suggest that the potentiating effects of rCGRP and SP might involve cholinergic receptors, as well as CGRP and tachykinin receptors, and that sCT, but not rCT, is able to mimic rCGRP in potentiating the secretion of fluid induced by SP.
Gen Pharmacol 1998 Jul
PMID:Effects of calcitonin and calcitonin gene-related peptide on the substance P-mediated secretion of fluid from the rat submandibular gland. 959 92

Previous research demonstrates that intraseptal administrations of arginine vasotocin (AVT) inhibit male aggression in the territorial field sparrow (Emberizidae: Spizella pusilla) but facilitate aggression in the colonial zebra finch (Estrildidae: Taeniopygia guttata). In order to determine whether this difference may be related to the territorial and colonial social organizations of these two species, the effect of AVT infusions was examined in a territorial Estrildid species, the violet-eared waxbill (Uraeginthus granatina). This species is more closely related to the zebra finch than to the field sparrow and shares most critical features of breeding ecology in common with zebra finches, but differs in social organization. AVT infusions administered via chronic guide cannulae directed at the septum significantly inhibited aggressive behavior, consistent with results in the territorial field sparrow, supporting the hypothesis that social organization is correlated with AVT function. Similar experiments with mesotocin and substance P produced no effects on any of the behaviors measured, but infusions of vasoactive intestinal polypeptide (VIP) significantly facilitated aggression. This result contrasts with the inhibitory effect of septal VIP obtained in the colonial zebra finch, suggesting that VIP function may be correlated with social organization as well.
Gen Comp Endocrinol 1998 Aug
PMID:Vasotocin and vasoactive intestinal polypeptide modulate aggression in a territorial songbird, the violet-eared waxbill (Estrildidae: Uraeginthus granatina). 967 95

Substance P and other polycationic peptides are thought to stimulate mast cell degranulation via direct activation of G proteins. We investigated the ability of extracellularly applied substance P to translocate into mast cells and the ability of intracellularly applied substance P to stimulate degranulation. In addition, we studied by reverse transcription--PCR whether substance P-specific receptors are present in the mast cell membrane. To study translocation, a biologically active and enzymatically stable fluorescent analogue of substance P was synthesized. A rapid, substance P receptor- and energy-independent uptake of this peptide into pertussis toxin-treated and -untreated mast cells was demonstrated using confocal laser scanning microscopy. The peptide was shown to localize preferentially on or inside the mast cell granules using electron microscopic autoradiography with 125I-labeled all-D substance P and 3H-labeled substance P. Cell membrane capacitance measurements using the patch-clamp technique demonstrated that intracellularly applied substance P induced calcium transients and activated mast cell exocytosis with a time delay that depended on peptide concentration (delay of 100-500 s at concentrations of substance P from 50 to 5 microM). Degranulation in response to intracellularly applied substance P was inhibited by GDPbetaS and pertussis toxin, suggesting that substance P acts via G protein activation. These results support the recently proposed model of a receptor-independent mechanism of peptide-induced mast cell degranulation, which assumes a direct interaction of peptides with G protein alpha subunits subsequent to their translocation across the plasma membrane.
J Gen Physiol 1998 Nov
PMID:Mechanism of peptide-induced mast cell degranulation. Translocation and patch-clamp studies. 980 67

1. Peptidylglycine alpha-amidating mono-oxygenase (PAM) is a bifunctional key enzyme in the bioactivation of neuropeptides. Its biosynthesis, distribution, functional role, and pharmacological manipulation are discussed. 2. PAM biosynthesis from a single gene precursor is characterized by alternative splicing and endoproteolytic events, which control intracellular transport, targeting, and enzyme activity. 3. The enzyme is mainly stored in secretory vesicles of many neuronal and endocrine cells with high abundance in the pituitary gland. Its functional role has been studied using enzyme inhibitors. Thus selective, peripheral PAM inhibition reduces substance P along with an anti-inflammatory action. 4. PAM-related pathologies are characterized by an increased relative abundance of alpha-amidated neuropeptides. To attenuate such hormone overproduction, novel, specific, and disease-targeted PAM inhibitors may be developed based on enzyme polymorphism.
Gen Pharmacol 1998 Nov
PMID:Peptidylglycine alpha-amidating mono-oxygenase: neuropeptide amidation as a target for drug design. 980 59

1. The effects of GR203040, a tachykinin neurokinin1 receptor antagonist, on tissue damage induced by X-irradiation (Rad) or cisplatin (Cisp) were investigated in ferrets. 2. GR203040 (0.3 mg/kg SC) reduced the Rad-induced plasma protein extravasation (PPE) in the duodenum and kidney by 25% in each tissue. 3. GR203040 (3 mg/kg SC, 5-min pretreatment and every 8 hr for 48 hr after Cisp) reduced the Cisp-induced PPE in the duodenum, jejunum and lung by 59, 52 and 60%, respectively. 4. Histological examination showed that GR203040 also ameliorated the Rad- and Cisp-induced tissue damage.
Gen Pharmacol 1998 Nov
PMID:Effects of GR203040, an NK1 antagonist, on radiation- and cisplatin-induced tissue damage in the ferret. 980 72

The sturgeons (order Acipenseriformes) are extant representatives of a group of ancient Actinopterygian (ray-finned) fish. Galanin and scyliorhinin I (a tachykinin with limited structural similarity to mammalian substance P) have been isolated from an extract of the gastrointestinal tract of a sturgeon (an F1 hybrid between the shovelnose sturgeon, Scaphirhynchus platorynchus, and the pallid sturgeon, Scaphirhynchus albus). The primary structure of sturgeon galanin (Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu10-Leu-Gly-Pro-His-Ala-Val -As p-Gly-His-Arg20-Ser-Leu-Ser-Asp-Lys-His-Gly-Leu-Pro.NH2) contains only two amino acid substitutions (Ser23 --> Asn and Pro29 --> Ala) compared with galanin from the bowfin, Amia calva (Amiiformes), but five amino acid substitutions compared with galanin from the trout (Teleostei). Similarly, the sturgeon tachykinin (Ser-Lys-Tyr-His-Gln-Phe-Tyr-Gly-Leu-Met.NH2) contains only one amino acid substitution (Tyr3 --> Ser) compared with scyliorhinin I previously isolated from bowfin stomach but five amino acid substitutions compared with trout substance P. The data support the hypothesis that the Acipenseriformes and the basal Neopterygians (gars and bowfin) share a close phylogenetic relationship.
Gen Comp Endocrinol 1999 Jan
PMID:Purification and characterization of galanin and scyliorhinin I from the hybrid sturgeon, Scaphirhynchus platorynchus x Scaphirhynchus albus (Acipenseriformes). 988 42

A peptide with substance P-like immunoreactivity was isolated from extracts of the brains of the pallid sturgeon, Scaphirhynchus albus and the North American paddlefish, Polyodon spathula. The primary structure of the peptide (Lys-Pro-Lys-Pro-His-Gln-Phe-Phe-Gly-Leu-Met.NH(2)) is the same in both species and contains 2 amino acid substitutions (Arg(1) --> Lys and Gln(5) --> His) compared with human substance P and 1 substitution (Arg(3) --> Lys) compared with substance P from the trout (Teleostei). Scyliorhinin I, a tachykinin previously isolated from an extract of sturgeon intestine, was not detected in either brain extract. A peptide with neurokinin A-like immunoreactivity (Ser-Ser-Ala-Asn-Arg-Gln-Ile-Thr-Gly-Lys(10)Arg-Gln-Lys-Ile-Asn-Ser-P he-Val-Gly-Leu(20)Met.NH(2)) was isolated from sturgeon brain and contains 10 amino acid substitutions compared with human neuropeptide gamma (a specific product of the posttranslational processing of gamma-preprotachykinin A) but only 4 substitutions compared with trout neuropeptide gamma. It was not possible to obtain the paddlefish neurokinin A-related peptide in pure form. The structural similarity between the sturgeon and the trout tachykinins supports the hypothesis that the Acipenseriformes (sturgeons and paddlefish) represent the sister group of the Neopterygii (gars, bowfin, and teleosts).
Gen Comp Endocrinol 1999 Oct
PMID:Tachykinins (substance P and neuropeptide gamma) from the brains of the pallid sturgeon, Scaphirhynchus albus and the paddlefish, Polyodon spathula (Acipenseriformes). 1052 58

Somatostatin (SRIF) binding sites were characterized in goldfish brain. Binding of (125)I-[Tyr(11)]-SRIF-14 to a brain membrane preparation was found to be saturable, reversible, and time-, temperature-, and pH-dependent. Binding was also displaceable by different forms of SRIF. Under optimal conditions (22 degrees C, pH 7.2), the equilibrium binding of (125)I-[Tyr(11)]-SRIF-14 to goldfish brain membranes was achieved after 60 min incubation. Analysis of saturable equilibrium binding revealed a one-site model fit with K(a) of 1.3 nM. SRIF-14, mammalian SRIF-28, and salmon SRIF-25 displaced (125)I-[Tyr(11)]-SRIF-14 binding with similar affinity, whereas other neuropeptides, e.g., substance P, were unable to displace (125)I-[Tyr(11)]-SRIF-14. Autoradiography studies demonstrated that (125)I-[Tyr(11)]-SRIF-14 binding sites are found throughout the goldfish brain. A high density of (125)I-[Tyr(11)]-SRIF-14 binding sites was found in the forebrain, including the nucleus preopticus, nucleus preopticus periventricularis, nucleus anterioris periventricularis, nucleus lateralis tuberis, nucleus dorsomedialis thalami, nucleus dorsolateralis thalami, nucleus ventromedialis thalami, and nucleus diffusus lobi inferioris. In midbrain, (125)I-[Tyr(11)]-SRIF-14 binding sites were found in the optic tectum. The facial and vagal lobes and the mesencephalic-cerebellar tract were found to have a high density of binding sites. This study provides the first characterization and distribution of specific binding sites for SRIF in a fish brain.
Gen Comp Endocrinol 2000 Jan
PMID:Characterization and distribution of somatostatin binding sites in goldfish brain. 1062 Apr 28


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