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)

Contribution of kallikrein-kinin system to heat-induced substance P (SP) release into the periphery was studied by using plasma kininogens-deficient strain Brown Norway Katholiek (B/N-Ka) and normal strain Brown Norway Kitasato (B/N-Ki) rats. Bradykinin (BK) and SP levels in the sc perfusates of the hind instep were measured by radioimmunoassay. In B/N-Ki rat, immersion of hind paw into hot water (47 degrees C) for 20 min led to an increase of BK (43 +/- s 34 fmol.min-1) and SP (11.1 +/- 9.7 fmol.min-1) in the perfusate, whereas those in B/N-Ka rat (BK 1.3 +/- 1.0 fmol.min-1 (P < 0.01), SP 5.5 +/- 3.5 fmol.min-1 (P < 0.05)) were remarkably less. Heat-induced extravasation (leakage of Evans blue) in B/N-Ka rat was also less than that in B/N-Ki rat (P < 0.05). Results suggest that kallikrein-kinin system is involved in the release of SP into the periphery, ie, BK released into the extravascular space by noxious heat stimulation intervenes in SP release.
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PMID:[Releases of bradykinin and substance P by heating hind paw of rat]. 752

Nitric oxide (NO) modulates myocardial contractile behavior in several isolated preparations, e.g., cardiac myocytes and papillary muscles, via elevation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We have recently reported that the exogenous NO donor, sodium nitroprusside, selectively modulates left ventricular (LV) relaxation in the isolated ejecting guinea pig heart, independent of coronary flow. We now report the effects of endogenously released NO on LV performance in this preparation (constant heart rate and loading). Both bradykinin (1 nM, n = 6) and substance P (100 nM, n = 6) accelerated early LV relaxation (maximum change in time constant, tE, -10.5 +/- 1.6 and -13.4 +/- 2.1%, respectively; both P < 0.05), without significantly altering early systolic parameters (e.g., rate of LV pressure development). These effects were inhibited by hemoglobin (P < 0.05; n > or = 6), which inactivates NO. Bradykinin (100 nM, n = 10) had an additional negative inotropic effect, which was not inhibited by hemoglobin. Neither agonist altered relaxation in isolated papillary muscles. These data suggest that endogenous NO, probably released from coronary microvascular endothelial cells, modulates LV relaxation in the intact heart.
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PMID:Modulation of left ventricular relaxation in isolated ejecting heart by endogenous nitric oxide. 752 13

1. We compared effects of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, on vasodilator responses to intra-arterial infusion of bradykinin and substance P in the human forearm. 2. Bradykinin (100 pmol min-1) increased forearm blood flow when infused into the brachial artery of eight healthy male volunteers, from 2.8 +/- 0.2 (mean +/- s.e. mean) to 9.3 +/- 1.0 ml min-1 per 100 ml forearm volume. 3. Co-infusion of L-NMMA (2 mumol min-1 and 4 mumol min-1) with bradykinin (100 pmol min-1) for 6 min produced respectively a 9 +/- 14% and 42 +/- 14% inhibition (compared with L-NMMA vehicle) in the response to bradykinin. 4. Substance P (1 pmol min-1) when infused into the brachial artery of a further eight male subjects increased forearm blood flow from 3.4 +/- 0.2 to 6.3 +/- 0.7 ml min-1 100 ml-1. 5. Co-infusion of L-NMMA (2 mumol min-1 and 4 mumol min-1) with substance P (1 pmol min-1) for 6 min produced respectively a 27 +/- 8% and 70 +/- 13% inhibition (compared with L-NMMA vehicle) in the response to substance P. 6. These results demonstrate that vasodilator responses to both bradykinin and substance P are mediated in part via the L-arginine/NO pathway. Bradykinin and substance P may be useful agonists with which to study endothelial function in this vascular bed.
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PMID:Effect of NG-monomethyl-L-arginine on kinin-induced vasodilation in the human forearm. 753 Apr 73

The present study examined the role of substance P (SP) as a sensory neurotransmitter in cardiovascular responses to bradykinin applied on the gallbladder. Experiments were performed in anesthetized cats in which sympathetic chains were transected at the T5-T6 level, and the tip of the intrathecal catheter was positioned at T6-T7 to limit the injectate between T6 and L2. Bradykinin (10 micrograms/ml) was applied onto the gallbladder before and after intrathecal injection of [D-Pro2,D-Phe7,D-Trp9]SP (100-200 micrograms, NK1/NK2-receptor antagonist), CP-99,994 (50-100 micrograms, selective NK1 antagonist), MEN-10,376 (100-500 micrograms, selective NK2 antagonist), or vehicle. Intrathecal injection of NK1 but not NK2 antagonist significantly reduced increases in mean arterial pressure, heart rate, and maximal rate of left ventricular pressure change by 28 +/- 2 mmHg (33 +/- 4%), 4 +/- 1 beats/min (42 +/- 5%), and 497 +/- 46 mmHg/s (36 +/- 4%), respectively. Intrathecal injection of NK1 or NK1/NK2 antagonist had no effect on cardiovascular responses evoked by electrical stimulation in the rostral ventral lateral medulla. These data suggest that endogenous SP, acting as a sensory neurotransmitter, is involved in the excitatory cardiovascular reflex caused by chemical stimulation of the gallbladder through its action on NK1 receptors in the spinal cord.
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PMID:Role of spinal NK1 receptors in cardiovascular responses to chemical stimulation of the gallbladder. 753 72

Reperfusion of the ischemic myocardium results in the loss of endothelium-dependent relaxation. We have shown recently that the alternate complement pathway is activated immediately on reperfusion of the ischemic porcine myocardium. We hypothesized that complement activation directly attenuates endothelium-dependent relaxation of porcine coronary arteries. Bradykinin (BK) or substance P concentration-dependently relaxed precontracted (U46619, 50 nmol/L) left anterior descending coronary artery (LAD) rings in vitro. Addition of zymosan to human (10%) or porcine (10%) serum for 30 minutes significantly (P < 0.05) increased the EC50 of BK-induced LAD relaxation from 4 +/- 1 to 418 +/- 159 nmol/L (n = 8) and from 9 +/- 3 to 281 +/- 132 nmol/L (n = 7), respectively. Similarly, addition of zymosan to 10% human serum (HS) for 30 minutes increased the EC50 of substance P-induced LAD relaxation from 0.4 +/- 0.1 to 30 +/- 14 nmol/L (n = 9, P < .05). Basal release of nitric oxide was reduced significantly in LAD rings exposed to zymosan-activated HS compared with HS alone. Addition of soluble CR1 (sCR1, 10 nmol/L) to zymosan-activated HS preserved BK-induced relaxation (EC50) of the LAD rings (control, 4 +/- 1 nmol/L; sCR1 + zymosan+serum, 2 +/- 1 nmol/L; n = 6). Zymosan-activated C8-depleted HS (10%) did not attenuate the EC50 of BK-induced coronary artery relaxation (3 +/- 1 to 3 +/- 1 nmol/L, n = 7, P = NS). Zymosan-activated C8-depleted HS plus C8 (6 micrograms/mL) increased the EC50 of BK-induced coronary artery relaxation from 4 +/- 1 to 423 +/- 141 nmol/L (n = 12, P < .05). We have further demonstrated that C5b-9 complexes can be found on the luminal surface of LAD endothelial cells after 5 minutes of exposure to zymosan-activated HS by using C5b-9 reactive monoclonal antibody fluorescent immunohistochemistry and confocal microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complement-mediated loss of endothelium-dependent relaxation of porcine coronary arteries. Role of the terminal membrane attack complex. 753 59

The purpose of this study was to determine the effects of bradykinin (BK), substance P (SP) and histamine on plasma exudation in the skin of conscious dogs with and without pacing-induced heart failure. We also determined the role tissue angiotensin I-converting enzyme (ACE) and neutral endopeptidase (NEP) play in modulating these responses. We found that intradermal injection of BK, SP and histamine induced a significant, concentration-dependent Evans blue exudation in normal dogs (p < 0.05). Bradykinin-induced responses were significantly potentiated by captopril (p < 0.05). In contrast, phosphoramidon potentiated BK-induced responses only at low concentrations of BK. Both captopril and phosphoramidon had no significant effects on SP- and histamine-induced Evans blue exudation. BK- and SP-induced responses were significantly attenuated, whereas histamine-induced Evans blue exudation was significantly potentiated in dogs with heart failure. We conclude that heart failure is associated with attenuation of BK- and SP-, but not histamine-induced plasma exudation in the peripheral microcirculation and that these responses are not modulated by tissue ACE and NEP.
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PMID:Plasma exudation in conscious dogs with experimental heart failure. 753 20

Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine, methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked in dorsal hind-paw skin by antidromic stimulation of the saphenous nerve, and in passive cutaneous anaphylactic reaction, bradykinin-, substance P-, compound 48/80-, histamine- and serotonin-induced ear edema. Indomethacin was ineffective in these respects. Bradykinin- and substance P-induced plasma exudation were also significantly reduced when [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin and substance P, respectively. In isolated rat peritoneal mast cell preparation, acetylshikonin produced a concentration-dependent inhibition of histamine and beta-glucuronidase release from mast cells challenged by compound 48/80. In compound 48/80-pretreated mice, acetylshikonin and isoproterenol produced significantly more inhibitory effect on bradykinin- and substance P-induced plasma exudation than did diphenhydramine in combination with methysergide. Pretreatment with diphenhydramine/methysergide in compound 48/80-pretreated mice significantly further reduced the bradykinin- and substance P-induced plasma exudation if [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin or substance P, respectively. The results suggest that the inhibitory effect of acetylshikonin on the edematous response is due neither to the release of steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably partly to the suppression of mast cell degranulation and partly to protection of the vasculature from mediator challenge.
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PMID:Inhibition of hind-paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin. 753 60

The ability of washed whole cells of Treponema denticola ATCC 35405 to hydrolyze (inactivate) substance P, bradykinin, and angiotensin I was studied. Substance P was attacked primarily at the Phe-8-Gly-9 bond by a chymotrypsin-like proteinase (CTLP), at Pro-4-Gln-5 by an endo-acting prolyl oligopeptidase (POPase), and at Gln-5-Gln-6 by an endopeptidase (FALGPA-peptidase). Bradykinin was cleaved at Phe-5-Ser-6 by the FALGPA-peptidase and at Pro-7-Phe-8 by the POPase. Angiotensin I was rapidly converted to angiotensin II by the CTLP, and both angiotensin I and angiotensin II were further hydrolyzed at Pro-7-Phe-8 by the POPase. All these enzymes were assumed to be cell associated and were easily extracted with a mild (0.05 to 0.1%) Triton X-100 treatment. Because it was conceivable that the hydrolysis of substance P at the Phe-8-Gly-9 bond was catalyzed by a CTLP described earlier (V.-J. Uitto, D. Grenier, E. C. S. Chan, and B. C. McBride, Infect. Immun. 56:2717-2722, 1988), the enzyme was purified to homogeneity by means of conventional fast protein liquid chromatography procedures. For kinetic studies, Phe-8(4-nitro)-substance P (NSP) (absorption maximum at 309.2 nm, epsilon = 545 M-1 cm-1) was synthesized to replace substance P as a substrate in kinetic studies. In reversed-phase chromatography, both NSP and substance P gave identical results with both whole cells and the purified enzyme. The CTLP has a mass of 95 kDa, and its activity is suggested to be based on an active seryl residue, on an active imidazole group, and on an active carboxyl group but not on metal cations. The enzyme hydrolyzes N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroaniline (SAAPFNA, a typical chymotrypsin substrate) at a high rate and several proteins, such as calf thymus histone, human plasma fibrinogen, milk caseins, and gelatin. Among the substrates tested, substance P showed the highest affinity (Km = 0.22 mM) for the purified enzyme. Depending on conditions, clinically applicable chlorhexidine levels (3.2 mmol/liter, or 0.2%) strongly activated (up to fourfold) the hydrolysis of SAAPFNA by whole cells and the purified CTLP. The hydrolysis of NSP by whole cells and purified CTLP was slightly inhibited by chlorhexidine. The results demonstrated the versatility and the effectiveness of the outer membrane of T. denticola in occasioning a rapid breakdown and inactivation of human bioactive peptides and other peptidolytic catalyses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of the chymotrypsin-like membrane-associated proteinase from Treponema denticola ATCC 35405 in inactivation of bioactive peptides. 754 86

1. The effect of bradykinin, capsaicin, substance P and low pH medium on plasma extravasation in the guinea-pig conjunctiva has been studied. Evans blue dye was measured in the conjunctiva after local instillation of the agents into the conjunctival sac. 2. Bradykinin (2-50 nmol), capsaicin (20-50 nmol) and substance P (0.5-5 nmol) caused a dose-dependent increase in plasma extravasation with the following order of potency: substance P > bradykinin = capsaicin. The effect of capsaicin (50 nmol) and substance P (5 nmol) was abolished by the tachykinin NK1 receptor antagonist, CP-99,994 (8 mumol kg-1, i.v.) (P < 0.01), whereas CP-100,263 (8 mumol kg-1, i.v.) the inactive enantiomer of CP-99,994 was without effect. CP-99,994 inhibited by 70% (P < 0.01) the effect of bradykinin. 3. The kinin B2 receptor antagonist, Hoe 140 (icatibant, 10 nmol kg-1, i.v.) abolished the response to bradykinin (50 nmol) (P < 0.01), but did not affect the responses to capsaicin (50 nmol) or substance P (5 nmol). Plasma extravasation induced by low pH medium (pH 1) was abolished by CP-99,994 (P < 0.01) and by Hoe 140 (P < 0.01). 4. The present findings suggest that: endogenous or exogenous tachykinins increase plasma extravasation in the guinea-pig conjunctiva by activation of NK1 receptors; bradykinin-induced plasma extravasation is mediated by tachykinin release from sensory nerve endings; low pH media cause plasma extravasation via release of kinins that by activation of B2 receptors release tachykinins from sensory nerve endings.
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PMID:Involvement of tachykinins in plasma extravasation induced by bradykinin and low pH medium in the guinea-pig conjunctiva. 754 95

We recently reported that alpha-adrenergic vasoconstriction is blunted and adenosine-induced vasodilation is enhanced in proximal coronary arteries of exercise-trained miniature swine [C. L. Oltman, J. L. Parker, H. R. Adams, and M. H. Laughlin. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H372-H382, 1992]. The purpose of the present study was to determine whether this model of exercise training also alters endothelium-dependent vasodilator responses of proximal coronary arteries. Female Yucatan miniature swine were exercise trained (ET) on a motor-driven treadmill or were cage confined (Sed) for 13-20 wk. Exercise tolerance, heart weight-to-body weight ratios, and skeletal muscle oxidative capacity were all significantly greater in ET than in Sed animals. Vasodilator responses were evaluated in vitro by determining concentration-response curves by using vascular rings (3.5-4 mm in axial length) isolated from right and left coronary arteries. Vasorelaxation responses were determined, after tone had been produced with either 30 microM prostaglandin F2 alpha, 30 mM KCl, or 30 nM endothelin. Concentration-response curves were obtained to endothelium-dependent vasodilators including bradykinin (10(-9)-10(-6) M), substance P (10(-12)-10(-6) M), clonidine (10(-9)-10(-6) M), serotonin (10(-10)-10(-5) M), and the Ca2+ ionophore A-23187 (10(-10)-10(-6) M). Endothelium-independent vasodilator responses to sodium nitroprusside (10(-9)-10(-4) M) were not different between arteries from Sed and ET. Bradykinin, substance P, and A-23187 were potent vasodilators in arteries from both groups, whereas serotonin and clonidine did not consistently produce vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-dependent vasodilation of proximal coronary arteries from exercise-trained pigs. 755 39


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