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. The isolated hepatic artery of the rabbit contracted to exogenously applied noradrenaline (NA). There was no significant difference in the maximal contraction or the EC50 value in vessels where the endothelium was present and in endothelium-denuded preparations. 2. Acetylcholine (ACh) induced a vasodilatation of vessels preconstricted with NA which was entirely dependent on the endothelium. 3. Adenosine 5'-triphosphate (ATP), 2-methylthio ATP, adenosine and sodium nitroprusside induced concentration-dependent, sustained relaxations of vessels in which tone had been induced with NA. The relaxation responses were not reduced after removal of the endothelium. 8-Phenyltheophylline antagonized the relaxation response produced by adenosine, but not that due to ATP at lower concentrations. The maximum response to ATP was reduced in the presence of 8-phenyltheophylline. 4. alpha,beta-Methylene ATP produced further contraction of vessels preconstricted with NA in both endothelium-denuded preparations and in vessels where the endothelium remained intact. 5. Immunohistochemical analysis was used to show the presence of nerve fibres containing substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) in the hepatic artery. Application of SP induced a concentration-dependent relaxation which was entirely dependent on the presence of an intact endothelium. CGRP and VIP, however, elicited concentration-dependent relaxations which were independent of the endothelium. 7. It is concluded that in the rabbit hepatic artery, responses to ACh are dependent on the presence of intact endothelium. P1-, P2x- and P2y-purinoceptors, mediating relaxation to adenosine, vasoconstriction to ATP and vasodilatation to ATP respectively, are located on vascular smooth muscle. Furthermore, CGRP and VIP mediate a direct vasodilatation of smooth muscle both in the absence and the presence of the endothelium, whereas SP produces a relaxation via receptors located on the endothelium.
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PMID:Endothelium-dependent and endothelium-independent vasodilatation of the hepatic artery of the rabbit. 171 28

Substance P (SP) stimulates polyphosphoinositide breakdown in the rat anterior pituitary through an NK-1 receptor. In the present study we present evidence that the coupling between the SP-NK1 receptor complex and polyphosphoinositide-specific phospholipase C (PI-PLC) in rat anterior pituitary membranes may involve a mechanism consistent with a GTP-binding protein. The formation of inositol phosphates from [3H]myo-inositol-labelled anterior pituitary membranes induced by SP was potentiated by GTP and non-hydrolysable guanine nucleotides. The stimulatory effects of SP alone and SP plus GTP could be blocked by addition of GDP-beta-S (guanosine 5-O-(thiodiphosphate] in excess. Basal and SP plus guanine nucleotide-induced inositol phosphate formation were stimulated by fluoride, whereas the effect of SP alone was inhibited. Pretreatment of anterior pituitary membranes with sodium deoxycholate attenuated the inositol phosphate response elicited by GTP and GTP-gamma-S, whereas basal and SP-stimulated inositol phosphate production showed a peak at 1 mg sodium deoxycholate/ml. SP, fluoride and guanine nucleotide stimulatory effects on hydrolysis of polyphosphoinositide (PPI) were unaffected by pretreatment of anterior pituitary cells with cholera or pertussis toxin for 12h. Treatment of anterior pituitary membranes with cholera and pertussis toxin yielded [32P]ADP-ribosylation of two proteins with molecular masses of 45 and 41 kDa respectively. We conclude that SP coupling to PI-PLC through the NK1 receptor in the rat anterior pituitary involves a GTP-binding mechanism distinct from the G-proteins associated with adenylate cyclase, Gs and Gi.
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PMID:Substance P stimulation of polyphosphoinositide hydrolysis in rat anterior pituitary membranes involves a GTP-dependent mechanism. 171 80

1. In isolated heart muscle preparations, selective removal of the endocardium results in a characteristic and unusual negative inotropic effect. Possible mechanisms for this effect were investigated in this study. 2. In endocardium-intact preparations of ferret papillary muscle, 8-bromo-cyclic GMP, sodium nitroprusside, atrial natriuretic peptide (ANP) and substance P each induced changes in contractile behaviour similar to selective endocardial removal, and each significantly elevated myocardial cyclic GMP levels. Substance P failed to elevate myocardial cyclic GMP levels following removal of endocardium or in the presence of haemoglobin, suggesting that it may act by releasing endothelium-derived relaxing factor (EDRF) from endocardium. However, there was no change in myocardial cyclic GMP levels following endocardium removal alone. 3. In cascade bioassay experiments, it was confirmed that porcine cultured endocardial cells released an unstable humoral agent whose effects on an endothelium-denuded pig coronary artery were indistinguishable from EDRF. 4. The negative inotropic effects of endocardium removal were reversed in bioassay experiments where an endocardium-denuded papillary muscle was exposed to the effluent from a column of porcine cultured endocardial cells on microcarrier beads. This demonstrates for the first time the release of a 'contraction prolonging factor' from endocardium, the tonic release of which would explain the negative inotropic effect of endocardium removal. 5. It is concluded that elevation of ferret papillary muscle cyclic GMP (as for example with EDRF) produces changes in contractile performance similar to those induced by endocardium removal. We also demonstrate that superfused porcine cultured endocardial cells release a humoral agent (provisionally named 'endocardin') which causes reversal of the changes in mechanical properties seen after endocardial removal.
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PMID:Factors released from endocardium of the ferret and pig modulate myocardial contraction. 171 74

The effects of angiotensin-converting-enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), substance P (SP-LI), calcitonin gene-related peptide (CGRP-LI), vasopressin (ADH-LI), atrial natriuretic peptide (ANP-LI) and renin activity (PRA) in patients with severe CHF (NYHA III-IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I-II). Catecholamines and NPY-LI were increased to the same extent in both groups with severe CHF. CGRP-LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP-LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP-LI level of 4.05 +/- 0.79 pmol l-1, compared to a concentration of 2.28 +/- 0.30 pmol l-1 (P less than 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP-LI and the serum sodium levels (r = -0.68, P less than 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH-LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP-LI levels was increased to a similar extent in both groups.
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PMID:Increased plasma level of substance P in patients with severe congestive heart failure treated with ACE inhibitors. 171 29

The mammalian tachykinins, substance P and neurokinin A, and the non-mammalian tachykinin, physalaemin, were tested on functionally identified dorsal horn neurones in vivo. The experiments were done on cats which were anaesthetized with sodium pentobarbital or were anaemically decerebrated. Extracellular single-unit recordings were made in the lumbar spinal cord and the tachykinins were applied by iontophoresis. Each neurone was classified functionally as wide dynamic range, non-nociceptive, nociceptive specific or proprioceptive. The response to tachykinin application was determined for each neurone. Application of each of the tachykinins evoked a characteristic excitatory response which was delayed in onset, slow in developing and prolonged: physalaemin excited 99/131 neurones tested, neurokinin A excited 45/63 neurones and substance P excited 32/49 neurones. With two neurones physalaemin evoked a depression of the rate of firing, which may have been caused indirectly by excitation of a neighbouring neurone. Such depression was not elicited by either substance P or by neurokinin A. Physalaemin had a preferential excitatory effect on nociceptive neurones evoking excitation of 76/94 nociceptive neurones compared with 12/23 non-nociceptive neurones (chi 2 = 7.9, 1 d.f., P = 0.005). Substance P also caused a preferential excitation, with 30/40 nociceptive neurones being excited while all of the non-nociceptive neurones (n = 7) were unaffected (chi 2 = 11.5, 1 d.f., P = 0.0007). In contrast, neurokinin A failed to have a preferential effect; 32/46 nociceptive and 9/10 non-nociceptive neurones were excited (chi 2 = 1.0, 1 d.f., P = 0.40). Comparing the proportions of nociceptive neurones excited by the different tachykinins indicated that this type of neurone was not differently sensitive to any of the three peptides (chi 2 = 3.2, 2 d.f., P = 0.20). On the other hand, non-nociceptive neurones were preferentially excited by neurokinin A and physalaemin compared with substance P (chi 2 = 13.4, 2 d.f., P = 0.001). With regard to the endogenous tachykinins the results of this study may be interpreted in the following ways. The differential excitatory effect of substance P on nociceptive neurones supports the proposed role for this peptide in the transmission specifically of nociceptive inputs at the first afferent synapse. On the other hand, as neurokinin A excited non-nociceptive as well as nociceptive neurones, there may be a functional role for neurokinin A distinct from that of substance P.
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PMID:Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P, neurokinin A and physalaemin. 171 88

Endoneurial hypoxia has been put forward as a factor contributing to diabetic neuropathy. The aim of this study was to determine whether alterations in motor nerve conduction velocity, Na+/K(+)-ATPase activity and substance P content of nerve and skin tissue, characteristic of the diabetic rat, could develop in non-diabetic animals subjected to a central hypoxaemia for five weeks. Compared to normoxic controls, five weeks of central hypoxaemia caused a fall in motor nerve conduction velocity of 30% (P less than 0.01), a decrease in sciatic nerve substance P content (68%; P less than 0.001) combined with elevated substance P content per unit area foot skin (44%; P less than 0.01). This pattern of change is qualitatively similar to that seen in diabetic rats. The Na+/K(+)-ATPase activity, however, was unaltered by the hypoxic environment. These findings support strongly a partial role for hypoxia in the pathogenesis of diabetic neuropathy.
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PMID:Central hypoxaemia in rats provokes neurological defects similar to those seen in experimental diabetes mellitus: evidence for a partial role of endoneurial hypoxia in diabetic neuropathy. 172 87

Mast cells of the human skin not only release mediators following immunological activation, but may also be stimulated to release histamine by the neuropeptides substance P, vasoactive intestinal polypeptide and somatostatin or by other basic secretagogues such as morphine, poly-L-lysine and compound 48/80. Release of histamine under these conditions is rapid and accompanied by minimal generation of the eicosanoids, prostaglandin (PG)D2 and leukotriene (LT)C4. Transient elevations of intracellular calcium are associated with mediator secretion induced by both stimuli, that induced by anti-IgE being derived from extracellular sources through channels in the plasma membrane while that stimulated by neuropeptides is mobilized intracellularly. Similarly, elevations of intracellular cyclic adenosine monophosphate (AMP) induced by anti-IgE occur only in the presence of extracellular calcium whereas with substance P elevations are apparent even in the absence of extracellular calcium. With the latter stimulus, histamine release is complete before the peak cyclic AMP is achieved. Histamine release stimulated by both secretagogues is unaffected by sodium cromoglycate or nedocromil sodium but is reduced by both salbutamol and isobutylmethylxanthine. Despite these biochemical and temporal differences, degranulation induced by both secretagogues proceeds by compound exocytosis which is indistinguishable under the electron microscope.
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PMID:Mediator secretion from human skin mast cells provoked by immunological and non-immunological stimulation. 172 14

Electrical stimulation at C4-C7 in the spinal canal of pithed guinea-pigs injected with atropine, d-tubocurarine and pentolinium caused frequency-dependent bronchoconstriction. Such non-cholinergic responses to electrical stimulation, unlike responses to substance P, were abolished by pretreatment with capsaicin but not by mepyramine or propranolol. Bronchoconstrictor responses to electrical stimulation were inversely related to rectal temperature (between 30-40 degrees C) whereas responses to substance P increased with increasing temperature over the same range. Ouabain (i.v.) augmented responses to electrical stimulation at 35-37 degrees C but depressed those at 30-32 degrees C. Both morphine and the alpha 2-adrenoceptor agonist B-HT920 (i.v.) inhibited non-cholinergic-mediated bronchoconstrictor responses at 30-32 degrees C. These results stress the importance of adequate control of body temperature in this preparation. Lowered body temperature may increase neuronal output of neuropeptides whilst depressing bronchial smooth muscle sensitivity. The data support previous conclusions regarding the role of Na+/K+ activated ATPase in temperature-induced changes in sensitivity to bronchoconstrictor stimuli.
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PMID:Hypothermia augments non-cholinergic neuronal bronchoconstriction in pithed guinea-pigs. 172 24

A cascade bioassay system has been used to quantify the basal and receptor-mediated endothelium-derived relaxing factor (EDRF) activity of pig coronary artery and pig renal artery. When exposed to EDRF released from a common donor vessel, pig coronary artery smooth muscle showed a greater sensitivity to EDRF than pig renal artery, and these differences were paralleled by differential responses to sodium nitroprusside. When mounted as donors in the bioassay, and EDRF detected using a common recipient, pig coronary artery and renal artery endothelium showed similar basal EDRF release rates. EDRF release in response to substance P was greater from pig coronary artery donors, but EDRF release in response to bradykinin was greater from pig renal artery donors. The data indicate that differences in EDRF response and EDRF release occur in different vessels, and that certain EDRF-releasing agents may exert regional vasodilator effects.
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PMID:A comparison of endothelium-derived relaxing factor activity in the coronary and renal arteries of the pig. 172 65

The present study investigated the sensitivity of the posterior part of the medial division of the bed nucleus of the stria terminalis (BNST) to the antinatriorexic action of the tachykinin eledoisin in the rat. Salt appetite was evoked by sodium depletion following furosemide-induced natriuresis. The results obtained show that bilateral injection of eledoisin into the BNST evokes a very potent antinatriorexic effect, a statistically significant inhibition being observed even at the dose of 3.1 ng/BNST. On the other hand, when eledoisin was injected into the lateral ventricle, just above the BNST, much larger doses were required to elicit comparable inhibition of salt appetite. The antinatriorexic effect of eledoisin into the BNST is apparently behaviorally selective, since the same doses, which inhibited salt appetite, did not significantly affect the intake of 10% sucrose solution in the sodium-depleted animal. Present results suggest that the BNST is a site of action for the effect of tachykinins on salt appetite.
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PMID:Bed nucleus of the stria terminalis: site for the antinatriorexic action of tachykinins in the rat. 181 84


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