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 presence of glutamate (Glu), aspartate (Asp) and substance P (SP) in the petrosal ganglion of rats anesthetized with pentobarbital sodium was studied using retrograde labeling of the carotid sinus nerve (CSN) with horseradish peroxidase (HRP) in combination with immunohistochemistry. (i) The incidence of HRP/Glu-labeled cells was the highest (32%, n = 3), followed in order by HRP/Asp-labeled cells (23%, n = 3) and HRP/SP-labeled cells (6%, n = 3). (ii) No significant difference was observed in the average diameter of HRP/Glu- and HRP/Asp-labeled cells, but the average diameter of HRP/SP-labeled cells was significantly larger than that of HRP/Glu- and HRP/Asp-labeled cells (P < 0.01). These results suggest that Glu may coexist with Asp, and SP-containing cells may form a different population from Glu- and Asp-containing cells in the petrosal ganglion. The physiological role of these transmitter substances is discussed.
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PMID:Transmitter substances contained in the petrosal ganglion cells determined by a double-labeling method in the rat. 128 28

The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret. 128 77

The relaxatory influences of substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) were investigated in human uterine arteries precontracted by noradrenaline in vitro. SP, VIP, CGRP and ANP all relaxed isolated uterine arteries with intact endothelium. When tested on vessels devoid of their endothelium VIP and SP had no effect on smooth muscular tone, while ANP and CGRP still induced unchanged vasodilatation. These results suggest an involvement of an endothelium-derived relaxing substance in the mechanisms by which VIP and SP induce relaxation of the isolated human uterine artery. On the other hand, ANP and CGRP seem to act on the same vessel preparation in vitro independently of the vascular endothelium. Both addition of noradrenaline and exchange of sodium against potassium in the organ chambers resulted in smooth muscle contraction irrespective of the integrity of the endothelium.
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PMID:Smooth muscle dilatation in the human uterine artery induced by substance P, vasoactive intestinal polypeptide, calcitonin gene-related peptide and atrial natriuretic peptide: relation to endothelium-derived relaxing substances. 128 18

It has been shown that endothelium-dependent vasorelaxation in response to muscarinic stimulation is attenuated in patients as well as animals with heart failure. This study aimed to determine if endothelium-dependent forearm vasodilation evoked with substance P (SP) as well as acetylcholine (ACh) was impaired in patients with heart failure. Forearm blood flow was measured using a strain-gauge plethysmograph and forearm vascular responses to intra-arterial infusions of ACh, SP, or sodium nitroprusside (SNP) at graded doses were examined. The drugs caused the dose-dependent increases in forearm blood flow (FBF) and the decreases in forearm vascular resistance (FVR) in patients with heart failure as well as normal subjects. However, the percent decreases in FVR by ACh were less in patients with heart failure than in normal subjects (p < 0.01). In contrast, the percent decreases in FVR by SP or SNP did not differ between the two groups. These results suggest that endothelium-dependent vasodilation of forearm resistance vessels via muscarinic receptors is specifically impaired, whereas via SP receptors, is preserved in patients with heart failure.
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PMID:Endothelium-dependent forearm vasodilation to acetylcholine but not to substance P is impaired in patients with heart failure. 128 77

The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG-nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG-nitro-L-Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI2 and PGE2) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance.
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PMID:The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart. 129 66

omega-Conotoxin GVIA, a peptide derived from the marine snail Conus geographus, is an antagonist of the neuronal N type voltage-sensitive calcium channels associated with neurotransmitter release. The present study investigated effects of this peptide on neurally mediated responses in airways isolated from the guinea pig to determine whether airway nerves are modulated by omega-conotoxin-sensitive calcium channels. Electrical field stimulation was used to induce neurally mediated tachykininergic excitatory responses in guinea pig bronchus and cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea. Exogenous agonists were administered to induce contractile (acetylcholine, substance P) or relaxation (sodium nitroprusside) responses. Tissues were incubated with omega-conotoxin (1 microM) or its vehicle (10 mM acetic acid) for 30 min before establishing frequency- or concentration-response relationships to the various stimuli. Frequency-response curves for neurally mediated cholinergic, nonadrenergic nocholinergic inhibitory and tachykininergic responses were shifted to the right by omega-conotoxin to a similar extent (4- to 5-fold). omega-Conotoxin had no effect on contractile responses elicited by exogenous acetylcholine or substance P or on relaxations induced by sodium nitroprusside. These findings indicate that neurotransmission in afferent tachykininergic kininergic nerves and in efferent cholinergic excitatory and nonadrenergic noncholinergic inhibitory nerves in the airways is modulated by a prejunctional omega-conotoxin-sensitive mechanism.
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PMID:Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways. 130 83

Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects.
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PMID:Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients. 131 88

Nedocromil sodium is a new chemical entity. This compound is very hydrophilic and is well absorbed by tissues such as the lung but not by tissues with tight junctions such as the gut. This product is chemically different from all drugs currently used for the treatment of airway diseases. The in vitro effects of nedocromil sodium are reviewed. Nedocromil sodium is capable of blocking: 1) the chemotaxis of neutrophils; 2) the activation of macrophages and monocytes by IgE; 3) the release of histamine from mast cells; 4) the cytotoxicity of platelets; 5) the release of LTC4 from eosinophils. Nedocromil sodium thus seems to have an effect on each of the cells which are implicated in the allergic reactions. In animals, nedocromil sodium can block the immediate bronchoconstriction induced by an antigen, adenosine and neurokinin A. Nedocromil sodium can also block the increase in bronchial responsiveness induced by antigen exposure. Moreover, vascular permeability induced by ovalbumin is reduced by nedocromil sodium. In summary, nedocromil sodium demonstrated a significant inhibitory effect of inflammation in both in vivo and in vitro models.
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PMID:[Basic research on nedocromil sodium]. 131 52

Repeated sodium depletions produce a persistent, enhanced need-free salt intake in the rat, particularly in the female. The neurochemical mechanisms underlying the phenomenon are still unknown. The present studies evaluated the effect on the enhanced need-free salt intake of the female rat (1) of pharmacological interference with the natriorexigenic hormones angiotensin II and aldosterone and (2) of the central injection of the tachykinin peptides, which are endowed with antinatriorexic activity. The need-free salt intake of the female rat is not modified by treatment with the angiotensin-converting enzyme inhibitor captopril or by the aldosterone receptor antagonist RU-28318. On the other hand, the behavior is highly sensitive to the inhibitory effect of central tachykinins, suggesting the possibility that need-free salt intake might be linked to modification (down-regulation) of the inhibitory tachykininergic system.
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PMID:Central tachykinin injection potently suppresses the need-free salt intake of the female rat. 132 51

Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides.
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PMID:A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. 132 27


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