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)

Coordinated release of relaxing and contracting factors from the endothelium modulates arterial distensibility. Recently, a similar release of the same and other factors from the coronary endothelium was shown to modulate myocardial performance in humans. This paracrine modulation of left ventricular (LV) performance by substances released from the coronary endothelium mainly affects diastolic LV function. This was evident from the reduction in end-systolic LV pressure, the earlier onset of LV relaxation and the increased LV diastolic distensibility observed in normal subjects during bi-coronary infusion of substance P. In experimental preparations, substance P elicited similar effects on diastolic LV function, which were attributed to a paracrine myocardial action of nitric oxide (NO) because they were absent after addition of hemoglobin. In normal subjects, the myocardial effects of NO were investigated during bi-coronary infusion of the NO-donor sodium nitroprusside and resembled the effects observed during bi-coronary infusion of substance P. This paracrine control of diastolic LV function by the coronary endothelium is influenced by substrate availability and by many neurohumoral substances, whose plasma levels are raised in heart failure. In transplant recipients, bi-coronary co-infusion of substance P and of L-arginine, the substrate for NO production, potentiated the fall in LV filling pressures. Pretreatment with intravenous dobutamine augmented the drop in LV end-systolic pressures observed during bi-coronary infusion of substance P. In isolated papillary muscles, a higher baseline myocardial c-GMP level, as induced by atrial natriuretic peptide, potentiates the negative inotropic and relaxation hastening effects of NO. In isolated ejecting guinea-pig hearts, an endothelin receptor antagonist improved diastolic LV function and this improvement implies paracrine myocardial action on diastolic LV function not only of NO but also of endothelin. Coronary endothelial control of myocardial function affects LV performance both acutely and chronically. An acute increase in heart rate augments release of NO because of coronary reactive hyperemia, lowers LV filling pressures thereby promoting subendocardial perfusion, and hastens LV relaxation thereby prolonging the diastolic time interval for coronary perfusion. Chronic changes in coronary endothelial function could also influence diastolic LV performance. Enhanced coronary endothelial NO release, as occurs during chronic exercise or pacing, could explain increased LV diastolic distensibility observed in athlete's heart and in tachycardia cardiomyopathy. Reduced endothelial NO release, as occurs with aging or after transplantation, could contribute to reduced LV diastolic distensibility in the elderly or in allograft recipients.
 ...
PMID:Paracrine coronary endothelial modulation of diastolic left ventricular function in man: implications for diastolic heart failure. 895 74

1. The relaxant of vasodilator peptides were examined in ring preparations of basilar arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. 2. Vasoactive intestinal peptide and peptide histidine isoleucine produced similar endothelium-independent relaxations in basilar arteries from WKY rats and SHRSP. Calcitonin gene-related peptide (CGRP) elicited endothelium-independent relaxations in both groups and the CGRP-induced relaxation was greater in SHRSP than in WKY rats. Substance P and neurokinin A did nor relax basilar arteries from either group. 3. Both WKY rat and SHRSP basilar arteries were relatively insensitive to atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide. 4. Bradykinin (BK) potently relaxed basilar arteries with endothelium, but BK produced contractions in endothelium-rubbed arteries in both WKY rats and in SHRSP. There was no significant difference in the relaxant response to BK between WKY rat and SHRSP arteries. 5. Adrenomedullin (AM) produced endothelium-independent relaxations in both groups and the relaxant response to AM was significantly greater in SHRSP than in WKY rats. 6. Human CGRP(8-37;mumol/L), a CGRP receptor antagonist, significantly inhibited both relaxant responses induced by CGRP and AM in WKY rats and in SHRSP arteries. 7. Among various peptides tested, the responses to CGRP and AM were higher in basilar arteries from SHRSP than in those from WKY rats. The relaxation produced by AM may be via CGRP receptors in WKY rat and SHRSP basilar arteries.
 ...
PMID:Relaxant effects of vasodilator peptides on isolated basilar arteries from stroke-prone spontaneously hypertensive rats. 907 89

Extracts from ragweed pollen grains contain novel trypsin and chymotrypsin-like serine peptidases which are described in this report. The molecular mass of the chymotrypsin-like enzyme was 82 kDa, had a pH optimum near 9.0, and its activity was unaffected by chelating or reducing agents. It was inhibited by diisopropyl fluorophosphate (DFP), a general serine class inhibitor, and more specifically N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a chymotrypsin-like proteinase inhibitor. In addition to various synthetic substrates, the neuropeptides, vasoactive intestinal peptide (VIP) and substance P, which are required for normalized lung functions, were also rapidly hydrolysed. Activity toward protein substrates was not detected with the exception of the inactivation of alpha-1-proteinase inhibitor (alpha-1-PI) which occurred through cleavage within the reactive site loop. The 'trypsin-like' enzyme has a molecular mass near 80 kDa, a blocked N-terminus, a pH optimum near 9.0, and requires Ca++ for stability and activity, but not reducing agents. It is inhibited by DFP, and more specifically the trypsin-like proteinase inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK). Again, activity toward protein substrates was not detected, but various synthetic substrates and biologically active peptides were efficiently cleaved. Significantly, atrial natriuretic peptide (ANP) and angiotensin 2 (ATII), whose degradation would amplify kinin activity and influence inflammatory diseases of the respiratory tract and nasal passages, were also rapidly hydrolyzed.
 ...
PMID:Ragweed pollen proteolytic enzymes: possible roles in allergies and asthma. 946 75

Plasma concentrations of vasoactive peptides have been reported to be influenced by various procedural features of hemodialysis (HD), such as ultrafiltration and isovolemic diffusion, dialysate buffer and dialysate temperature, but also by sham HD thus reflecting an effect of the extracorporeal circulation per se. In the present study the effect of heparin administration was investigated in 9 stable HD patients, and compared with that of saline. Blood samples were taken from the arteriovenous fistula before and 45 min after the administration of heparin or saline. After an interval of 2 weeks, the procedure was repeated with the exception that the patients who received heparin on the first occasion were given saline and vice versa. Plasma concentrations of the vasoactive peptides were measured by radioimmunoassay. Regardless of whether heparin was given or not, the plasma concentrations of the vasodilators atrial natriuretic peptide, beta-endorphin and vasoactive intestinal peptide did not change, nor did the concentration of the vasoconstrictor neuropeptide Y. The plasma motilin concentration decreased significantly when heparin was given, and that of substance P increased, both these peptides being vasodilators. Mean arterial blood pressure decreased regardless of whether heparin was given or not, and no difference between the two regimens was noted. Heart rate was unchanged with both regimens. To sum up, administration of heparin but not of saline affected the plasma concentrations of motilin and substance P. However, the decrease in blood pressure during the procedure seemed not to be related to the changes in these peptides, as it also occurred in the absence of heparin.
 ...
PMID:Heparin and vasoactive peptides in hemodialysis patients. 968 Nov 55

Immunohistochemistry of normal eccrine sweat glands was performed on paraffin sections of human skin. Immunoreactivity (ir) for neuron specific enolase, S100 protein (S100), regulatory peptides, nitric oxide synthase type I (NOS-I) and choline-acetyltransferase (ChAT) was found in small nerve bundles close to sweat glands. In the glands, secretory cells were labelled with anticytokeratin antibody. Using antibodies to S100, calcitonin gene-related peptide (CGRP) and substance P (SP) a specific distribution pattern was found in secretory cells. Granulated (dark) and parietal (clear) cells were immunopositive for CGRP, and S100 and SP, respectively. Immunoreactivity was diffuse in the cytoplasm for CGRP and S100, and peripheral for SP. Myoepithelial cells were not labelled. Electron microscopy revealed electron dense granules, probably containing peptide, in granulated cells. Using antibodies to NOS-I and ChAT, ir was exclusively found in myoepithelial cells. Immunoreactivity for the atrial natriuretic peptide was absent in sweat glands. These results provide evidence for the presence of both regulatory peptides involved in vasodilation and key enzymes for the synthesis of nitric oxide and acetylcholine in the secretory coil of human sweat glands. It is suggested that human sweat glands are capable of some intrinsic regulation in addition to that carried out by their nerve supply.
 ...
PMID:Immunohistochemical evidence suggests intrinsic regulatory activity of human eccrine sweat glands. 1038 80

The expression of selected regulatory neuropeptides was investigated by immunohistochemistry in nerves supplying the vomeronasal organ (VNO) of mice during postnatal development. Results show that neurons in the VNO are devoid of immunolabeling with any of the antibody used from 1 day to 2 months of age. In the non-receptor epithelium (NRE) and the vomeronasal vascular pump (VP) the timing of expression of regulatory neuropeptides differed among neuropeptides and the different VNO structures. Regulatory neuropeptides usually found in sensory nerves (substance P, calcitonin gene-related peptide) and efferent nerves (neuropeptide Y, atrial natriuretic peptide) are expressed in the NRE and the VP, respectively. These results support the view that the VNO is to some extent functional during postnatal development.
 ...
PMID:Neuropeptide expression in the mouse vomeronasal organ during postnatal development. 1042 68

Studies on the distribution of peptides in human tissues have been made either by measuring responses to localized stimuli or by subjecting extracts of different regions to radioimmunoassay (RIA). Attempts at isolating regulatory peptides from the mammalian tissues have resulted in the isolation of many bioactive fragments. Later, modification of initial isolation methods led to the identification of the native molecules in various tissues and body fluids. The present study examined atrial natriuretic peptide (ANP) and several other peptides in cardiac tissues of several species of laboratory mammal and human beings; using a sensitive and highly specific radioimmunoassays. In all the species studied, ANP-like immunoreactivity appeared to be highest in the heart tissue of rat. The peptide was highest in the right atrium (RA) of rat and lowest in the RA of guinea pig (P< 0.002). Neuropeptide Y (NPY) another abundant cardiac peptide was present in the cardiac tissues of all species but was more in the left atrium (LA) than the RA of all species (P<0.05). Calcitonin gene-related peptide (CGRP) was present throughout the cardiovascular system of the rat and guinea pig. Small but detectable amount of Neurotensin (NT) immunoreactivity was found in the rat but was consistently negative in the guinea pig cardiac tissues (P< 0.05). Substance P (SP) immunoreactivity was detected in the rat and higher quantities being in the Aorta but no trace of the peptide was detected in the left ventricle, aorta nor the pulmonary vein of post mortem human. Though the structure of most of the species studied has been elucidated, the primary structure of guinea pig ANP has not been fully generated. Thus the data obtained may suggest that in keeping with these mammalian peptides, the primary structures may be variant. With most of the peptides studied (e.g. ANP, Neuropepdide Y), immunoreactivity occurs predominantly in the atrial tissues, but is also present in vessels outside the heart, a finding which may be of functional significance.
 ...
PMID:Regulatory peptides in the heart and major vessels of man and mammals. 1065 87

Vascular resistance in the mammalian pulmonary circulation is affected by many endogenous agents that influence vascular smooth muscle, right ventricular myocardium, endothelial function, collagen and elastin deposition, and fluid balance. When the balance of these agents is disturbed, e.g. by airway hypoxia from high altitude or pulmonary obstructive disorders, pulmonary hypertension ensues, as characterized by elevated pulmonary artery pressure (P(PA)). Among neuropeptides with local pulmonary artery pressor effects are endothelin-1 (ET-1), angiotensin II (AII), and substance P, and among mitigating peptides are calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), atrial natriuretic peptide (ANP), vasoactive intestinal peptide (VIP) and ET-3. Moreover, somatostatin28 (SOM28) exacerbates, whereas SOM14 decreases P(PA) in hypoxic rats, with lowering and increasing of lung CGRP levels, respectively. Pressure can also be modulated by increasing or decreasing plasma volume (VIP and ANP, respectively), or by induction or suppression of vascular tissue remodeling (ET-1 and CGRP, respectively). Peptide bioavailability and potency can be regulated through hypoxic up- and down- regulation of synthesis or release, activation by converting enzymes (ACE for AII and ECE for ET-1), inactivation by neutral endopeptidase and proteases, or by interaction with nitric oxide (NO). Moreover, altered receptor density and affinity can account for changed peptide efficacy. For example, upregulation of ET(A) receptors and ET-1 synthesis occurs in the hypoxic lung concomitantly with reduced CGRP release. Also, receptor activity modifying protein 2 (RAMP2) has been shown to confer ADM affinity to the pulmonary calcitonin-receptor-like receptor (CRLR). We recently detected the mRNA encoding for RAMP2, CRLR, and the CGRP receptor RDC-1 in rat lung. The search for an effective, lung selective treatment of pulmonary hypertension will likely benefit from exploring the imbalance and restoring the balance between these native modulators of intrapulmonary pressure. For example, blocking of the ET-1 receptor ET(A) and vasodilation by supplemental CGRP delivered i. v. or via airway gene transfer, have proven to be useful experimentally.
 ...
PMID:The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. 1119 57

Angiotensin-converting enzyme (ACE) is mainly responsible for converting angiotensin I (AI) to angiotensin II (AII), and ACE inhibitors prevent atherosclerosis in animal models. Neutral endopeptidase 24.11 (NEP) degrades substance P, kinins and atrial natriuretic peptide (ANP), and aortic wall NEP activity was found to be increased in atherosclerosis. In the present study, we have evaluated the effect of candoxatril, a NEP inhibitor, and of omapatrilat, a dual ACE and NEP inhibitor, on the development of fatty streak in apolipoprotein E (apoE)-deficient mice. Groups of ten male apoE-deficient mice were given either placebo, candoxatril 50 mg/kg per day, or omapatrilat 10, or 100 mg/kg per day for 4 months. None of the treatments influenced body weight, serum total or HDL-cholesterol. Compared with the placebo, candoxatril did not protect the mice from fatty streak deposit. In contrast, omapatrilat dose dependently inhibited the constitution of fatty streak in apoE-deficient mice. The precise advantages of the dual ACE and NEP inhibition versus the inhibition of only ACE should now be considered in the prevention of atherosclerosis as well as in the occurrence of its complications.
 ...
PMID:Omapatrilat, a dual angiotensin-converting enzyme and neutral endopeptidase inhibitor, prevents fatty streak deposit in apolipoprotein E-deficient mice. 1125 98

Neutral endopeptidase (NEP) is a zinc metallopeptidase ubiquitously distributed in various tissues in mammals. This peptidase is involved in the post-secretory metabolism of various neuropeptides and peptide hormones in vivo, such as enkephalins, bradykinin, atrial natriuretic peptide, substance P and endothelins. In this paper we show that NEP is expressed in ovaries as a 110-kDa glycosylated integral membrane protein with enzymatic properties similar to those of the kidney protein. Using immunohistochemistry, we localize the peptidase in the granulosa cells of follicles at all stages of maturation, with the exception of atretic follicles. We also observe immunoreactive staining in the epithelia that lines the blood vessels in the medulla and the surface of the ovary. The co-localization of NEP and bioactive peptides known to be physiological substrates of NEP in other tissues suggests an important role for this protein in processes such as follicle maturation, ovulation, and/or regulation of ovarian blood flow, by modulating the physiological function of these peptides.
 ...
PMID:Neutral endopeptidase is expressed on the follicular granulosa cells of rabbit ovaries. 1143 41


<< Previous 1 2 3 4 5 6 7 Next >>