Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250-350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1-100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.
 ...
PMID:Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways. 769 Jul 43

The effects of various muscarinic antagonists on acetylcholine (ACh)-induced pulmonary oedema were studied in isolated perfused rabbit lungs. ACh induced a dose-dependent increase in the capillary filtration coefficient (Kf,c). This effect has been previously related to the activation of the capsaicin-sensitive nerve fibres and the release of substance P. Atropine, pirenzepine (M1-selective antagonist) and 4-DAMP (M3-selective antagonist) altered this response, producing a dose-dependent shift to the right of the ACh concentration-Kf,c response curve. By contrast, the M2-selective antagonist AFDX-116 shifted the ACh concentration-response curve to the left. Atropine, pirenzepine and 4-DAMP also significantly reduced the capsaicin-induced increase in the Kf,c, while AFDX-116 enhanced it. We conclude that multiple muscarinic receptor subtypes are present in the rabbit lung, located on the C-fibres, and are involved in the ACh-induced pulmonary oedema. M1 and M3 receptors seem to stimulate the release of neuropeptides from C-fibres, whereas M2 receptors have an inhibitory effect on these fibers.
 ...
PMID:Multiple muscarinic receptor subtypes mediating pulmonary oedema in the rabbit. 782 37

1. We characterized the tachykinin receptor(s) mediating 'sensory-efferent' neural control of release of 35SO4-labelled macromolecules (mucus) from ferret trachea in vitro in Ussing chambers using selective tachykinin antagonists. Secretion was induced by substance P (SP), neurokinin A (NKA), capsaicin, the NK1 tachykinin receptor agonist [Sar9, Met(O2)11]substance P ([Sar9]SP), or acetylcholine (ACh), or by electrical stimulation of nerves. Antagonists used were FK888 and L-668,169, selective for the NK1 receptor, SR 48968, selective for the NK2 receptor, and FK224, a dual antagonist at NK1 and NK2 receptors. The selectivity of FK888 and SR 48968 was examined on NKA-induced contraction of ferret tracheal smooth muscle in vitro. 2. SP (1 microM) increased mucus secretion by 695% above vehicle controls. FK888 (0.1 microM-30 microM) inhibited SP-induced secretion in a dose-dependent manner, with complete inhibition at 10 microM and an IC50 of 1 microM. L-668,169 (1 microM) also completely inhibited SP-induced secretion. 3. NKA (1 microM) significantly increased mucus secretion by 271% above baseline, a response which was completely inhibited by FK888 (10 microM) or L-668,169 (microM). Secretion induced by ACh (10 microM: 317% above baseline) was not inhibited by FK888 but was inhibited by atropine. Capsaicin (10 microM)-induced secretion (456% above vehicle controls) was significantly inhibited by FK888 and by L-668,169 (111% and 103% inhibition respectively). 4. Electrical stimulation (50 V, 10 Hz, 0.5 ms, 5 min) increased mucus output above baseline (increased by 12 to 26 fold), a response blocked by tetrodotoxin (0.1 microM). FK888 (10 microM) inhibited the increase in secretion due to electrical stimulation by 47%. Atropine, propranolol and phentolamine in combination(APP) inhibited the response to electrical stimulation by 48%. The remaining NANC response, i.e. in the presence of APP, was further reduced by 66% with FK888. FK224 (10 microM) inhibited neurally evoked secretion by 73%. SR 48968 (0.1 fLM) had no effect on electrically-stimulated or [Sar9]SP-induced secretion.5. NKA (10nM- 1O microM: in the presence of DMSO control vehicle) induced tracheal smooth muscle contraction in a concentration-dependent manner with a maximal contraction of 30% of the maximal response to ACh (10 mM) and an ECm of 0.3 JAM. SR 48968 (0.1 microM in DMSO) inhibited the NKA induced contraction whereas FK888 did not. Neither antagonist had any inhibitory effect on ACh induced contraction.6. We conclude that 'sensory-efferent' neurogenic mucus secretion in ferret trachea in vitro is mediated via tachykinin NK, receptors with no involvement of NK2 receptors. Potent and selective tachykinin antagonists may have therapeutic potential in bronchial diseases such as asthma and chronic bronchitis in which neurogenic mucus hypersecretion may be aetiologically important.
 ...
PMID:'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro. 788 71

This study has examined the abilities of (+/-)-CP96345 and (+/-)-SR48968, nonpeptide antagonists selective for the tachykinin NK1 and NK2 receptors, respectively, to block bronchoconstriction caused by intravenous administration of direct-acting receptor agonists and the indirect-acting mimetics capsaicin, serotonin and 2-methyl-serotonin in the anesthetized guinea pig. The NK1 antagonist (+/-)-CP96345 was found to cause, at a maximally tolerated dose of 9 mumol/kg, an approximate 10-fold rightward shift of the dose-response curves for selective NK1 agonists substance P (SP), [Sar9,Met(O2)11]SP and Ac-[Arg6,Sar9,Met(O2)11]SP6-11 without altering responses to selective NK2 agonists neurokinin A (NKA), [Nle10]NKA4-10 or [beta-Ala8]NKA4-10. The NK2 antagonist (+/-)-SR48968 caused dose-dependent rightward shifts of the dose-response curves for the NK2 but not the NK1 agonists. Results using combinations of the receptor antagonists indicate that the NK2 agonists could cause bronchoconstriction by acting on the NK1 receptors at large doses relative to those used without antagonists. Of the agonists used here, [beta-Ala8]NKA4-10 appeared to be the most selective for the NK2 receptors. When used alone, only (+/-)-SR48968 was found to block bronchoconstriction caused by capsaicin, serotonin (after blockade of 5-HT2 receptors by LY53857) and 2-methyl-serotonin. When (+/-)-CP96345 was also given, larger additional blockade was seen with capsaicin than with serotonin or 2-methyl-serotonin as mimetic substance. Atropine caused small and variable degrees of blockade of serotonin and 2-methyl-serotonin but not of capsaicin after combinations of the two antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differential blockade by tachykinin NK1 and NK2 receptor antagonists of bronchoconstriction induced by direct-acting agonists and the indirect-acting mimetics capsaicin, serotonin and 2-methyl-serotonin in the anesthetized guinea pig. 826 78

Cholinergic neurons play a major role in the control of striatal activity via muscarinic receptors. The action of acetylcholine also appears to be dependent on the striosome-matrix compartmentalization of the striatum. This study was designed to find out whether modification of acetylcholine tone activates neurons in the striatum and forebrain of the rat. We looked for the appearance of immunoreactivity to Fos, a regulatory protein that is thought to convert synaptic signals into changes in gene expression. Pharmacological manipulation of muscarinic receptors was found to induce specific patterns of Fos immunoreactivity in distinct neuronal populations of the forebrain, including the striatum. Oxotremorine, a non-selective muscarinic agonist, induced Fos immunoreactivity in the striatum with a large predominance in striosomes (mostly in enkephalinergic neurons), in layers 4 and 6 of the cortex, and also in the piriform cortex and septum. The muscarinic agonist pilocarpine had an identical effect in the cortex, but the striosomal prevalence was less clear-cut than that observed after oxotremorine. Treatment with dopamine-depleting agents (6-hydroxydopamine or reserpine) and inhibitors of glutamate and opiate receptor (MK-801 and naloxone respectively) had no effect on the action of oxotremorine. This suggests that the induction of Fos provoked by oxotremorine does not involve dopamine, glutamate or opiates. Atropine, a non-specific muscarinic antagonist, also induced Fos immunoreactivity in the striatum but with matrix predominance (mostly in substance P neurons), as well as in the cingulate cortex, and the olfactory tubercle. Scopolamine, a muscarinic antagonist, induced Fos in both striosomal and matrix compartments in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fos immunoreactivity after stimulation or inhibition of muscarinic receptors indicates anatomical specificity for cholinergic control of striatal efferent neurons and cortical neurons in the rat. 828 24

1. The contractile responses to angiotensin II, angiotensin III and two synthetic analogues, [Lys2]angiotensin II and [Sar1]angiotensin II, in the guinea-pig isolated longitudinal muscle preparation of small intestine have been characterized in vitro. 2. Tachyphylaxis to the angiotensin analogues was reduced by use of a Krebs-Henseleit solution containing a raised (sub-contractile) concentration of potassium (11.2 mM). Under these conditions. reproducible cumulative concentration-response curves to all agonists were established. The pD2 estimates for angiotensin II, [Lys2]angiotensin II, angiotensin III and [Sar1]angiotensin II were 9.15 +/- 0.14, 7.42 +/- 0.06, 7.69 +/- 0.18 and 9.50 +/- 0.15 respectively and the maximum responses achieved were not significantly different. 3. The contractile responses to angiotensin II, angiotensin III and [Sar1]angiotensin II were reduced by greater than 80% by tetrodotoxin (TTX; 0.1 microM). However, the responses to [Lys2]angiotensin II were reduced by only 63 +/- 5%. Atropine (0.1 microM) also reduced the responses to angiotensin II, angiotensin III and [Lys2]angiotensin II, although its effect was less than that produced by TTX. Furthermore, while responses to these agonists were not significantly modified by the NK1 receptor antagonist (+/-)-CP-96,345 (30 nM) alone, the combined pre-incubation with both atropine and (+/-)-CP-96,345 reduced maximum agonist responses to a level not significantly different from those produced by TTX. 4. Indirect and direct contractile responses to angiotensin II and [Lys2]angiotensin II (in the presence of TTX) respectively were characterized by use of the selective AT1 receptor antagonist, losartan and the AT2 receptor antagonist, PD123177. Losartan produced parallel rightward displacement of the concentration-response curve to angiotensin II and [Lys2]angiotensin II, with an estimated pKB of 8.56(8.42-8.68) and 9.18 (8.63-9.50) respectively. The AT2 receptor antagonist, PD123177 (3 microM) failed to modify the contractile responses to either angiotensin II or [Lys2]angiotensin II.5. We conclude that two populations of angiotensin II receptors exist in the guinea-pig longitudinal muscle of small intestine, one located neuronally mediating the release of both acetylcholine and substance P and the other located on the smooth muscle mediating direct contractile responses. The neuronal component provides the major contribution to the agonist responses. Both receptor populations are of the AT1 receptor subtype.
 ...
PMID:Pharmacological characterization of the contractile responses to angiotensin analogues in guinea-pig isolated longitudinal muscle of small intestine. 848 24

This study was conducted to determine whether drug-dependent changes in cytosolic Ca2+ concentration take place in the ciliary nonpigment epithelial cells of rabbits under more physiological conditions. Iris-ciliary body from pigmented rabbits in organ-culture was loaded with a Ca(2+)-sensitive fluorescent dye, fura-2, and a video-imaging system with an image analyzer was employed. Using this method fluorescence from nonpigmented epithelial cells can be analyzed without interference from fluorescence from pigmented ciliary epithelial cells. Among the drugs studied, norepinephrine and carbachol induced Ca2+ transients in the nonpigmented epithelial cells of organ-cultured ciliary processes. Epinephrine, isoproterenol, dopamine, neuropeptide Y, and substance P at the concentration of 10(-6) to 10(-3) M failed to elicit a response. The cytosolic free Ca2+ concentration of the cells in the resting state, as determined by an in vitro calibration curve, was 166 nM. The peak free cytosolic Ca2+ concentration induced by norepinephrine was about 263 nM, and that induced by carbachol was more than 1,000 nM. The carbachol-induced response was larger in magnitude and longer in duration than that induced by norepinephrine. Not uncommonly, the carbachol-induced response lasted more than 15 min. The response was diminished in both peak height and duration by chelation of extracellular Ca2+. Atropine abolished the response showing the response being mediated by a muscarinic receptor.
 ...
PMID:Drug-dependent Ca2+ mobilization in organ-cultured rabbit ciliary processes. 852 97

The pharmacological mechanisms involved in the substance P (SP)-induced pulmonary oedema were studied in isolated perfused rabbit lungs. Substance P induced a dose-dependent increase in the capillary filtration coefficient (Kf,c), responsible for oedema. Atropine, hemicholinium-3 and ruthenium red pretreatment partly protected the lungs against SP effects, while tetrodotoxin and hexamethonium did not significantly modify them. (+/-)CP96,345, a NK1 receptor antagonist, completely inhibited the SP-induced increase in the Kf,c. Like SP, acetylcholine (ACh) and capsaicin also increased the Kf,c. Atropine and (+/-)CP96,345 completely blocked the oedema induced by both drugs. Tetrodotoxin and ruthenium red strongly inhibited the response to capsaicin and acetylcholine. It was concluded that SP-induced pulmonary oedema is in part mediated by a stimulating action on cholinergic efferent nerves, with subsequent release of endogenous acetylcholine. Acetylcholine can, in turn, stimulate the release of SP from excitatory non adrenergic, non cholinergic nerves. The effects induced by capsaicin and exogenous acetylcholine, thus endogenous SP, involve tetrodotoxin-sensitive mechanisms, while those produced by exogenous SP are tetrodotoxin-resistant.
 ...
PMID:Mechanisms of substance P-induced pulmonary oedema in the rabbit: interactions between parasympathetic and excitatory NANC nerves. 861 9

Jejunal motility measured manometrically and coupled fluctuations in electrogenic ion transport measured as transmural potential differences (PD) were simultaneously studied in ferrets infected with enteric stages of the parasitic nematode, Trichinella spiralis. Vagotomy in uninfected ferrets abolished jejunal motility clusters and associated PD oscillations. Conversely, in infected ferrets on days 8-12 postinfection (PI), vagotomy did not abolish jejunal motility and PD. Calculated motility indexes (MI) indicated that postvagotomy MI decreased to 12% of prevagotomy MI in uninfected ferrets, whereas, in T.spiralis-infected ferrets, postvagotomy MI declined only to 48% of prevagotomy MI. Atropine abolished all vagotomy-resistant residual jejunal motility clusters and PD oscillations in T. spiralis-infected ferrets. Decreased intestinal content of substance P (27% of control) and vasoactive intestinal peptide (41% of control) and increased myeloperoxidase activity (262% of control) were detected in T. spiralis-infected ferrets. Our results suggest that integrated neural control of muscular and epithelial effectors in the small bowel is altered by nematode-induced inflammation.
 ...
PMID:Neural integration of jejunal motility and ion transport in nematode-infected ferrets. 876 Jan 6

We previously demonstrated in an ex vivo rat tracheal model that chymotryptic activity is an index of mast cell degranulation and that substance P (SP) and electrical field stimulation (EFS) synergistically degranulate mucosal and connective tissue mast cells. In the current study, we found that the facilitatory effect of SP was apparent at concentrations as low as 10(-9) M. This effect was mimicked by 10(-7) M neurokinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor antagonist CP-96,345. SP + EFS-induced mast cell secretion was significantly attenuated by 10(-6) M tetrodotoxin. The response was also attenuated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxy-dopamine. Atropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS-induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-discharged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.
 ...
PMID:Substance P enhances electrical field stimulation-induced mast cell degranulation in rat trachea. 876 24


<< Previous 1 2 3 4 5 6 7 8 9 10