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)

Synovial tissue was obtained from 18 knees with medial compartmental osteoarthritis (OA) and from 20 knees on which a high tibial osteotomy had been performed. Neuropeptides were stained with a specific avidin-biotin-peroxidase method. Comparisons were made of the incidence of staining as well as the location of staining within the synovia (medial, lateral, and suprapatellar regions). The results showed that the synovium had an extensive neural network of both the somatic and autonomic nervous systems. In the medial synovium of the preoperative knees, the neuropeptides were found in abundance. An especially strong response for substance P (SP) and calcitonin gene-related peptide (CGRP) was observed at the free nerve endings. However, the postoperative incidence of SP-positive free nerve endings was reduced to 54% of the preoperative amount and the inflammation subsided in the medial region. These findings suggested that free nerve endings containing SP might be mainly involved in the inflammation and pain of OA.
Nihon Seikeigeka Gakkai Zasshi 1992 Sep
PMID:[Immunohistochemical study on the effect of high tibial osteotomy on the distribution pattern of neuropeptides in the synovium of the osteoarthritic knee]. 144 24

Twenty patients were selected on the basis of perennial rhinitis, the absence of allergy and with an eosinophil count higher than 20% of total leucocytes in nasal secretions (NARES). Nasal endoscopy with biopsies from the middle turbinate and sinus CT were performed. Biopsies were processed for histological examination and for immunofluorescence. The clinical progress during treatment was scrutinized. An acute congestive aspect of the nasal mucosa was noted in 4 cases, and micropolyposis in 9 cases. Sinus CT showed opacity of the ethmoidal cells in 87% of cases (maxillary sinuses: 75%; frontal sinus: 46%; sphenoidal sinus: 31%). An eosinophilic infiltrate of the nasal mucosa was constituted in 9 cases: In 6 cases, the cells expressed the Fc epsilon RII receptor, recognized by the monoclonal antibody Bb10. Anti-H1 drugs usually failed to result in a clinical improvement and local eosinophilia was not changed. Local corticoids were more effective but not sufficient in some cases, so that oral corticotherapy was needed. Ethmoidectomy was performed in three cases. NARES seems to evolve in three stages: (1) migration of eosinophils from the vessels to the secretions; (2) retention of eosinophils in the mucosa which might be linked to activation of unknown origin; (3) nasal polyposis. Numerous interactions between irritation of the epithelium, release of substance P, and eosinophils, lead to the hypothesis of a neurogenic origin of NARES.
Rhinology 1992 Sep
PMID:NARES: a model of inflammation caused by activated eosinophils? 144 72

1. The effects of chemically induced convulsions, clinically similar to those elicited by electroconvulsive treatment (ECT), on brain regional distribution of neuropeptide Y-, neurokinin A-, substance P- and neurotensin-like immunoreactivities were studied in the rat. 2. Pentylenetetrazole (PTZ) and bicuculline (BIC) were used to induce grand mal seizures. Rats were divided into three groups receiving one of the following treatments: Saline, PTZ (45 mg/kg) or BIC (1.5 mg/kg). 3. After sacrifice by focused microwave irradiation, brains were dissected, peptides extracted and measured by specific radioimmunoassays. 4. Repeated grand mal convulsions induced by PTZ, in similarity to ECT, markedly increased NPY-LI concentrations in frontal cortex and hippocampus. In contrast to ECT, no changes in NKA- or SP-LI levels were seen. NT-LI was lowered in striatum. 5. Bicuculline effects were more circumscribed: some animals developed grand mal and died while convulsing (peptides not measured), others did not develop generalized seizures and were sacrificed after the fourth treatment. 6. The results demonstrate a similar effect of PTZ and ECT on regional NPY-LI concentrations and raise the possibility that grand mal, regardless of etiology, is necessary for effects on peptides.
Prog Neuropsychopharmacol Biol Psychiatry 1992 Sep
PMID:Brain neuropeptides: changes by treatment with the convulsants pentylenetetrazole and bicuculline. 149 30

Neurons expressing the m1, m2, and m4 muscarinic receptor genes in the adult rat striatum were identified and characterized by using several in situ hybridization and immunohistochemical procedures. Combined in situ hybridization for the simultaneous detection of two mRNAs in the same section or in adjacent sections as well as in situ hybridization and immunohistochemistry on adjacent sections permitted us to identify the neurons containing m1, m2, or m4 receptor mRNA. Our observations demonstrate that m1, m2, and m4 receptor genes are expressed in one or several phenotypically distinct neuronal populations. The m1 receptor gene was the most widely expressed (85% of the striatal neurons). Most cholinergic neurons (80% or more) contain m1, m2, and m4 receptor mRNAs. Almost all the substance P neurons contain m1 and m4 receptor mRNA. All enkephalinergic neurons contained m1 receptor mRNA, but only 39% contained m4 receptor mRNA. Most somatostatin and neurotensin neurons expressed the m1 receptor gene, but only a few (15% and 9%, respectively) contained m4 receptor mRNA. The present study offers anatomical evidence that ACh may act directly in complex ways on the main neuronal populations of the striatum through muscarinic receptors. The m1, m2, and m4 receptors may act as autoreceptors to control ACh release and possibly other parameters of ACh neurons. On the other hand, the m1 and m4 receptors may act as heteroreceptors in cholinoceptive efferent neurons (enkephalin and substance P neurons) and other neurons (somatostatin/neuropeptide Y and neurotensin neurons). The presence of m4 receptor mRNA in only parts of the enkephalin, somatostatin, and neurotensin neuronal populations indicates that muscarinic receptor gene expression contributes to the functional and anatomical heterogeneity of the striatum that may relate to higher order of organization, including patch-matrix compartmentalization. The wide expression of m1 and m4 receptor genes in the striatum suggests that ACh may directly influence neurotransmitter release and synthesis in striatal efferent and intrinsic neurons. Our results imply that the specific pattern of expression of the muscarinic receptor genes mediates direct effects of ACh on activities and functions of chemically and topologically defined striatal neuronal populations. Since the expression of muscarinic receptors occurred in the three main neuronal populations of the striatum, namely ACh, enkephalins, and substance P neurons that also express dopamine receptors, it is highly probable that ACh and dopamine may act together at the single-cell level to influence striatal functions.
J Neurosci 1992 Sep
PMID:Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. 152 98

Transmural electrical stimulation and nicotine produced a relaxation of dog cerebral artery strips denuded of endothelium, which was abolished by tetrodotoxin and hexamethonium, respectively, and also suppressed by treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor. The inhibition was reversed by L-arginine but not by the D-enantiomer. L-NA also suppressed the endothelium-dependent relaxation by substance P but not the response to NO and nitroglycerin. Treatment with high concentrations of nitroglycerin or sodium nitroprusside markedly inhibited the relaxant response to nicotine, substance P and NO but not the response to papaverine. Slight, slowly developing relaxations caused by L-arginine in the endothelium-denuded arteries were not potentiated by repeated applications of the amino acid or by exposure of the strips for 24 hr to the bathing medium. Ca++ ionophore-induced contractions in the denuded strips were not potentiated by L-NA. Nicotine significantly increased the level of cyclic GMP in the arteries without endothelium; the increment was abolished by treatment with L-NA and hexamethonium. NO does not seem to be synthesized in smooth muscle in an amount sufficient to produce significant relaxation. It may be concluded that NO liberated from vasodilator nerves activates guanylate cyclase in smooth muscle and produces cyclic GMP, resulting in cerebroarterial relaxation.
J Pharmacol Exp Ther 1991 Sep
PMID:Role of nitric oxide in neurally induced cerebroarterial relaxation. 165 33

The amyloid beta protein (ABP) has been shown to interact with the substance P (SP) receptor in a cell culture model that may mimic the pathogenesis of Alzheimer's disease. In the present study, however, 4 fragments of ABP (beta 1-42, beta 1-16, beta 17-28, and beta 25-35) failed to interact with SP-induced Ca2+ mobilization in SP receptor-expressing cultured cells. Therefore, the action of these ABP-related peptides in our cultured cells is unrelated to the SP receptor.
Brain Res Mol Brain Res 1991 Sep
PMID:Amyloid beta protein substituent peptides do not interact with the substance P receptor expressed in cultured cells. 166 16

1. The ability of cromakalim to modulate several different types of neuroeffector transmission has been assessed in guinea-pig isolated trachea. 2. In trachea treated with propranolol (10(-6) M) and indomethacin (2.8 x 10(-6) M), stimulation of the extrinsic vagal nerves evoked contractions which were blocked by hexamethonium (5 x 10(-4) M) or by tetrodotoxin (TTX; 10(-6) M). Cromakalim (10(-5) M) caused a two fold rightward shift of the frequency-response curve. 3. In carinal trachea treated with propranolol and indomethacin, transmural stimulation evoked an initial, rapid contraction followed by a more sustained secondary contraction. The initial, rapid contractile response was virtually ablated by atropine (10(-6) M) or by TTX but was resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) caused a concentration-dependent rightward shift of the frequency-response curve for the initial contraction. 4. In carinal trachea treated with atropine, propranolol and indomethacin, transmural stimulation evoked only the secondary (non-adrenergic, non-cholinergic (NANC] contractile responses. These were markedly reduced by TTX but were resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) suppressed the NANC contractile responses in a concentration-dependent manner. This action could be offset by glibenclamide (10(-6) M). 5. In trachea treated with atropine, histamine (10(-4) M), propranolol and indomethacin, transmural stimulation evoked NANC relaxant responses. Cromakalim (up to 10(-5) M) was without effect on the frequency-response curve for the stimulation of NANC inhibitory nerves. 6. Tested on trachea bathed by drug-free Krebs solution, cromakalim (10(-7)-10(-5) M) caused concentration-dependent suppression of tracheal tone. In trachea treated with propranolol and indomethacin, cromakalim (10- 7-1O- 5 M) caused concentration-dependent antagonism of acetylcholine (ACh). In trachea treated with atropine, propranolol and indomethacin, cromakalim (up to 10- 5M) failed to antagonize effects of either histamine or substance P.7. It is concluded that cromakalim can inhibit cholinergic (excitatory) neuroeffector transmission in the trachea but only at a concentration having demonstrable inhibitory activity against the action of exogenous ACh and the spontaneous tone of the airways smooth muscle. In contrast, cromakalim may depress NANC excitatory (putative peptidergic) neuroeffector transmission at a concentration below that exerting inhibitory activity on airways smooth muscle. Cromakalim does not concurrently depress NANC inhibitory neuroeffector transmission. Depression of NANC excitatory neuroeffector transmission could explain the ability of cromakalim to suppress airway hyperreactivity or bronchial asthma at doses lacking direct relaxant effect on airways smooth muscle.
Br J Pharmacol 1991 Sep
PMID:Effects of cromakalim on neurally-mediated responses of guinea-pig tracheal smooth muscle. 166 64

1. We have evaluated the biological activity of a number of neurokinin A (4-10), (NKA (4-10)) analogues in the endothelium-deprived rabbit isolated pulmonary artery (RPA) and hamster isolated trachea (HT), two tissues rich in different NK2 receptor subtypes. 2. MDL 28,564, a pseudopeptide selective for NK2 receptor sites, behaved as a full agonist in the RPA, while in the HT it competitively antagonized NKA or [beta Ala8]-NKA (4-10) contractile effects. 3. The peculiar behaviour of MDL 28,564 in the RPA and HT may be explained neither by a difference in receptor reserve between the two organs (the reserve being three times greater in RPA than in the HT) nor by a different affinity for the two receptor subtypes (identical dissociation constants, pKA or pKB, calculated in the RPA and in the HT). On the other hand, MDL 28,564 displayed a very different intrinsic efficacy for the two receptor subtypes. 4. The novel peptides MEN 10,295 ([Trp7, beta Ala8]-NKA-(4-10)) and MEN 10,296 ([Tyr5, Trp7, beta Ala8]-NKA-(4-10] behaved as weaker agonists than MDL 28,564 in the RPA, but retained appreciable agonist activity also in the HT. 5. The novel peptides: MEN 10,282 ([Tyr5, D-Trp6,8, Trp9, Arg10]-NKA-(4-10], MEN 10,449 ([diI-Try5, D-Trp6,8,9, Arg10]-NKA-(4-10] and the cyclic hexapeptide L 659,877 (cyclo [Leu-Met-Gln-Trp-Phe-Gly]) behaved as competitive antagonists against NKA contractile effects both in the RPA and HT. MEN 10,282 and MEN 10,449 were unable to distinguish between the NK2 receptor subtypes, having almost the same affinity in the two organs. On the other hand L 659,877 was about 15 times more potent in the HT than in the RPA. 6. These results provide further evidence for NK2 receptors heterogeneity and are useful in outlining pharmacological features of the two subtypes present in the RPA and HT.
Br J Pharmacol 1991 Sep
PMID:Further evidence for the existence of NK2 tachykinin receptor subtypes. 166 68

pA2 values of new B2 receptor antagonists ranging from 7.51 to 8.86 were measured on the rabbit jugular vein, while lower values were observed in the other preparations (for instance, the hamster urinary bladder). The most potent antagonists were those containing a hydroxyproline (Hyp) in position 3, a D-Arg at the N-terminal and a Leu instead of a Phe in position 8, with or without other chemical changes. D-Arg[Hyp3,D-Phe7,Leu8]-BK was found to be competitive, selective for B2 receptors and specific for kinins since it was without effect against substance P and angiotensin II in the rabbit jugular vein. The essential feature for obtaining B2 receptor antagonists appears to be the replacement or reorientation of Phe8 of bradykinin. The rabbit jugular vein provides a sensitive bioassay in which the potency and specificity of B2 receptor antagonists can be adequately evaluated.
Agents Actions 1991 Sep
PMID:New highly potent bradykinin B2 receptor antagonists. 166 87

The release of endogenous noradrenaline (NA) from slices of adult rat brainstem and ventral thoracic spinal cord was investigated using a fixed-volume incubation technique and HPLC with electrochemical detection. Incubation with potassium (15-50 mM) produced a dose-related increase in basal NA release that was calcium dependent. The potassium-evoked release of NA from spinal cord or brainstem slices was potentiated according to dose by preincubation with either (a) the selective alpha 2-adrenoceptor antagonist idazoxan (10(-6)-10(-4) M) or (b) the thyrotrophin-releasing hormone (TRH) analogue RX 77368 (pGlu-His-3,3'-dimethyl ProNH2; 10(-5) and 10(-4) M). Incubation of spinal cord slices with the NA uptake inhibitor maprotiline (1 microM) enhanced the effect of idazoxan but inhibited that of RX 77368. The effects of RX 77368 and potassium alone (15 mM) on NA release from both spinal cord and brainstem slices were reduced to basal levels with tetrodotoxin (10(-7) M). Similarly, preincubation of spinal cord, but not brainstem, slices with the insect neuropeptide proctolin (10(-4) M) significantly attenuated the potassium- or RX 77368-induced release of NA, whereas substance P (3 X 10(-5) and 1 X 10(-4) M) had no effect on either tissue. These results suggest that changes in NA release in the spinal cord and brainstem may mediate some of the actions of neuropeptides in ventral spinal cord, although the peptides may not be acting directly on the noradrenergic nerve terminals in these tissues.
J Neurochem 1991 Sep
PMID:Ventral horn neuropeptides modulate the release of noradrenaline from tissue slices of rat brainstem and ventral thoracic spinal cord. 167 77


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