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)

Ciliostimulation induced by various transmitters has been suggested to be mediated by the release of nitric oxide (NO). Freshly obtained adenoid tissue explants were pre-treated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro L-arginine (L-NNA), to determine whether the ciliostimulators terbutaline, methacholine, substance P, and endothelin-1 require the release of NO to increase ciliary beat frequency (CBF) in vitro. The L-NNA pre-treatment affected the change in CBF induced by each of the ciliostimulators tested. To determine whether cyclic nucleotides also stimulate CBF by inducing the release of NO, an extra series of experiments were performed with dibutyryl cAMP and dibutyryl cGMP, and L-NNA pre-treatment. In contrast to the experiments with the various ciliostimulators, both dibutyryl cAMP and dibutyryl cGMP exerted ciliostimulatory effects that could not be inhibited by L-NNA. The present findings suggest that NO acts as an intermediate messenger in the ciliated epithelium in response to various transmitters and mediators. On the other hand, pre-treatment with the NOS inhibitor L-NNA did not affect ciliary response to the second messengers cAMP and cGMP, thus suggesting that NO dependent mechanisms do not constitute the sole pathway for the stimulation of ciliary function.
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PMID:Ciliostimulatory effects mediated by nitric oxide. 1068 41

Endothelin has previously been localised in perivascular nerves of the rat basilar artery. Considering its potent vasoconstrictor and mitogenic properties on vascular smooth muscle, the potential role of a neural source of this peptide in hypertension has been investigated. The trigeminal, superior cervical and sphenopalatine ganglia of Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 16 weeks of age have been examined for immunolocalisation of endothelin at the light and electron microscope level. At the light microscope level, neurones immunopositive for endothelin were detected in these ganglia of the SHR but were not seen in ganglia from WKY rats. This difference was particularly marked in the trigeminal ganglia where endothelin-positive neurones colocalised with substance P immunoreactivity. Using in situ hybridisation techniques, endothelin-1 mRNA was localised to the cytoplasm of neurones in the ganglia and was more prominent in the SHR. At the electron microscope level, endothelin-immunoreactivity was localised at the peripheral perikarya of some neuronal cell bodies of the trigeminal, superior cervical and sphenopalatine ganglia of WKY rats but was more prominent with heavy labelling throughout the cytoplasm of neurones in the SHR. Notably, in the trigeminal ganglia of the SHR only, some endothelin-immunopositive nerve fibres appeared to be damaged and contained vacuoles with granular material. Ultrastructural examination of the basilar artery revealed an increased number of endothelin-positive axons in the SHR, but these axons usually showed selective damage. In summary, in the SHR, there was a marked increase in endothelin particularly in sensory neurones projecting to the basilar artery which also appear to be undergoing degenerative changes. An increased neural source of endothelin in the SHR may contribute to the development of hypertension or may be a consequence of selective degenerative change.
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PMID:Neural endothelin in hypertension: increased expression in ganglia and nerves to cerebral arteries of the spontaneously hypertensive rat. 1072 Aug 85

This study investigated the vasorelaxant action of the sesquiterpene polygodial, isolated from the bark of Drymis winteri, on rat portal vein in vitro, contracted by various agonists. Polygodial (21-342 microM) preincubated 20 min before, produced graded antagonism of the contractile responses caused by bradykinin, endothelin-1, noradrenaline, the stable analogue of thromboxane A2 U46619, substance P, neurokinin B, and senktide (an NK3-selective agonist). Polygodial, at the same concentration, also produced graded inhibition of the contractile response induced by potassium chloride and by phorbol ester. At the median inhibitory concentration (IC50) level, polygodial was approximately 114- to 177-fold more active in inhibiting mediated contractions to senktide and phorbol ester. When assessed in the tonic contraction induced by endothelin-1 (0.5 nM) or by phorbol (3 microM), polygodial (0.1-100 microM) produced concentration-dependent relaxation, with maximal inhibition (E(max)) of 62 +/- 2% and 100%, respectively. Finally, polygodial (0.1-100 microM) inhibited the rhythmic spontaneous contractions of the rat portal vein (E(max) of 75 +/- 2%). Taken together, these results suggest that the vasorelaxant actions caused by polygodial in rat portal vein are, at least in part, associated with inhibition of calcium influx through voltage-sensitive channels and interaction with protein kinase C-dependent mechanisms. In addition, these data confirm and extend our previous suggestion that polygodial preferentially antagonizes tachykinin-mediated contraction, especially the NK3-mediated responses.
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PMID:Action of polygodial on agonist-induced contractions of the rat portal vein in vitro. 1077

Vasomotor responses to various agonists were studied on isolated circular segments of human epicardial coronary arteries from three different age groups; 23-38 years, 40-58 years and 63-86 years. Noradrenaline had no or only weak contractile effect on coronary arteries from younger patients but induced contraction of all artery segments from older patients. The Emax value was significantly (P<0.0001) higher in arteries from the oldest group compared to each of the two younger age groups, whereas the potency was similar in all three groups. Linear regression analysis of noradrenaline-induced contraction in individual patients revealed a significantly positive age-correlation (correlation coefficient 0.67, P<0.0001). Contraction induced by endothelin-1 and relaxation induced by substance P, calcitonin gene-related peptide and vasoactive intestinal peptide on arteries precontracted with U46619 showed no significant differences in maximum responses and potencies between the three age groups, and no significant linear age-correlation. These data demonstrate a large variability in contractile responses to noradrenaline with contractions seen mostly in coronary arteries from older patients. It thus seems that sympathetic activation could contribute to coronary ischaemia in some patients.
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PMID:Influence of ageing on vasomotor responses of human epicardial coronary arteries. 1081 52

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.
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PMID:Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins. 1112 9

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.
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PMID:The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. 1119 57

Experiments were conducted to delineate the vascular effector systems that contribute to setting mesenteric vascular tone in swine during the first postnatal month. Terminal mesenteric arteries (TMA), which function as resistance vessels, were studied in vitro with a microvascular perfusion system allowing independent pressure and flow manipulation. When pressure was varied 0-100 mmHg in the absence of flow, TMA from 1-day-old animals demonstrated myogenic vasoconstriction, whereas TMA from 40-day-old animals did not. In 1- but not 40-day-old TMA, the endothelin A (ET(A)) receptor antagonist BQ-610 shifted the pressure-diameter curve upward, whereas the ET(B) receptor antagonist BQ-788 and the L-arginine analog N(G)-monomethyl-L-arginine (L-NMMA) shifted the curve downward; in all instances, myogenic vasoconstriction was preserved. Flow eliminated myogenic vasoconstriction in 1-day-old TMA, i.e., diameter increased as a function of pressure. The effect of BQ-610 was lost under flow conditions; however, BQ-788 and N-acyl-L-Trp-3,5-bis-(trifluoromethyl) benzyl ester, an antagonist specific to the substance P neurokinin-1 (NK(1)) receptor, shifted the pressure-diameter curve downward in the presence of flow, whereas L-NMMA restored myogenic vasoconstriction. Adding flow had no effect on the pressure-diameter relationship in 40-day-old TMA. Other blocking agents, including prazosin, losartan, indomethacin, and charybdotoxin, had no effect on the pressure-diameter relationship in either age group under flow or no-flow conditions. Constitutive production of nitric oxide (NO) and endothelin-1 participates in setting resistance in 1-day-old TMA, and important stimulants to NO production include flow and activation of ET(B) and NK(1) receptors. In contrast, 40-day-old TMA act as passive conduits in which the elastic properties of the vessel are the primary determinant of diameter.
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PMID:Determinants of terminal mesenteric artery resistance during the first postnatal month. 1125 94

Information is sparse concerning the effect of oophorectomy (OOX) on bone vascularization and blood flow of possible significance for altered remodeling. Whether OOX affects functional characteristics of isolated bone resistance arteries was investigated. Ring preparations (diameter approximately 250 microm) of small femoral bone arteries from oophorectomized and sham-operated rabbits were mounted on a myograph six weeks postoperatively. Cumulative concentration response curves were obtained for various agonists at a normalized lumen diameter. Oophorectomy did not significantly influence lumen diameter, maximal response to high potassium, or maximal response to high potassium and 10(-5) M noradrenaline. However, OOX significantly increased the maximal response to noradrenaline (OOX 2.14 +/- 0.36 N/m, Sham 1.25 +/- 0.14 N/m) and endothelin-1 (OOX 1.76 +/- 0.32, Sham 0.95 +/- 0.15) in metaphyseal arteries. Moreover, the corresponding maximal active pressure for the agonists was significantly increased. OOX did not influence endothelial function assessed by the effects of acetylcholine or substance P. The functional responses of diaphyseal arteries were unaffected by OOX. The study demonstrates regional differences in the effects of OOX on small arteries of importance for control of vascular resistance in bone which suggests a relation between altered vascular function after ovarian hormonal withdrawal and the changes in bone turnover associated with osteoporosis.
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PMID:Effects of oophorectomy on functional properties of resistance arteries isolated from the cancellous bone of the rabbit femur. 1139 51

1. In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse trachea and in human isolated airway preparations. 2. We investigated the role of secondary mediators in ET-1 induced potentiation of cholinergic nerve-mediated contraction in human bronchi, in particular the possible role of neuropeptides in this phenomenon. 3. Bronchial tissues after endothelin treatment were exposed to a standard electrical field stimulation (EFS) (30% of EFS 30 Hz)-induced contraction. In addition, in some experiments, preparations were treated with a tachykinin NK(2) receptor antagonist and subsequently exposed to the same protocol. HPLC and RIA were performed on organ bath fluid samples. Moreover, the human bronchi were used for the beta-PPT (preprotachykinin) mRNA extraction and semiquantitative reverse transcription polymerase chain reaction (RT - PCR), prior to and 30-40 min following ET-1 challenge. 4. The selective tachykinin NK(2) receptor antagonist, SR48968, was effective to reduce ET-1 potentiation of EFS mediated contraction. HPLC or RIA showed significant increased quantities of NKA in organ bath effluents after EFS stimulation in bronchi pretreated with ET-1. Finally, beta-PPT mRNA level after stimulation of bronchi with ET-1 was increased about 2 fold respect to control untreated bronchi. 5. In conclusion, this study demonstrated that, at least in part, the ET-1 potentiation of cholinergic nerve-mediated contraction is mediated by tachykinin release, suggesting that in addition to nerves, several type of cells, such as airway smooth muscle cell, may participate to neuropeptide production.
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PMID:Endothelin-1 increases cholinergic nerve-mediated contraction of human bronchi via tachykinin synthesis induction. 1172 50

Changes in responsiveness of the vas deferens and urinary bladder to bradykinin (BK) receptor agonists (Tyr8-BK and des-Arg9-BK), substance P (SP), and endothelin-1 (ET-1) were assessed 8 weeks after streptozotocin (STZ)-induced diabetes. Preparations from control or STZ-treated (60 mg/kg i.p.) male rats were tested for contractile and neurogenic twitch potentiating (TP, in VD only) effects of all four agonists (1 nM to 0.3 or 3 microM). In diabetic VD, contractile effects of Tyr8-BK, des-Arg9-BK, and SP were enhanced, but ET-1 effects were unchanged. In contrast, TP by des-Arg9-BK was unaffected, that by Tyr8-BK was decreased, and those by SP and ET-1 were increased. In diabetic UB, only contractions to des-Arg9-BK and SP were enhanced. Following insulin replacement (human, 1-3 U/day s.c.), starting 1 week after STZ, TP induced by Tyr8-BK and des-Arg9-BK in VD were further inhibited, but all other changes in both preparations were reversed at least partially. Insulin treatment of nondiabetic rats, however, also affected VD (but not UB) responsiveness, such that contractions to Tyr8-BK and TP by ET-1 were increased, but TP by Tyr8-BK was decreased. Thus, STZ-induced type I diabetes causes important alterations in responsiveness of non-vascular smooth muscle tissues of the rat to BK, SP, and ET-1. Long term insulin replacement, at doses normalising glycaemia, effectively reversed most changes in VD or UB responsiveness, but it is unclear if this is truly due to blocking of STZ-induced changes, since the treatment also affected responsiveness of nondiabetic tissues.
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PMID:Diabetes-induced changes in responsiveness of rat bladder and vas deferens to peptides in vitro: susceptibility to reversal by insulin. 1202 69


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