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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the sympathetic nervous system and of arginine vasopressin (AVP) in the mediation of the central cardiovascular effects of angiotensin II (ANG II) and substance P (SP) was investigated. ANG II and SP caused dose-dependent blood pressure increases when injected into the lateral brain ventricle (i.c.v.) of conscious rats; ANG II was tenfold more potent than SP. Peripheral blockade of alpha-adrenoceptors with prazosin or blockade of the vasopressor action of AVP by the AVP antagonist d(CH2)5VDAVP both partially inhibited the pressor responses to central ANG II. Combined treatment with the two blockers produced almost complete inhibition of the central ANG I responses. Substance P injected i.c.v. produced increases in noradrenaline and adrenaline but not AVP in the plasma. Peripheral alpha-receptor blockade by prazosin reversed the central pressor effects of SP to depressor responses. The AVP antagonist did not alter the cardiovascular responses to SP. It is concluded that in conscious animals, stimulation of the sympathetic nervous system and release of AVP contribute to the central pressor action of ANG II to a similar extent and independently of each other. In contrast, the central pressor responses to SP appear to be exclusively mediated by the sympathetic nervous system without participation of AVP.
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PMID:Central blood pressure effects of substance P and angiotensin II: role of the sympathetic nervous system and vasopressin. 616 92

The effect of six hypothalamic peptides on the basal release of ACTH and that induced by arginine vasopressin (AVP) or by ovine corticotrophin releasing factor (oCRF) from fragments of the rat anterior pituitary gland incubated in vitro was investigated. Dose-response curves to AVP and to oCRF were obtained, and the response to a low dose of oCRF was potentiated by a low dose of AVP. Basal release of ACTH was not affected by any of the peptides in concentrations in the range 10(-12) to 10(-6) mol/l, and only substance P (SP) and somatostatin (SRIF) inhibited significantly the response to oCRF in a dose-related manner. The responses to a range of doses of oCRF or AVP were reduced by 10(-8) and 10(-6) mol SP or SRIF/l, and to a greater extent by the higher dose. Except in the case of 10(-6) mol SRIF/l on the response to AVP, the response was not further diminished by preincubation of the tissue with the peptide before the stimulating agent was added. The inhibition of the responses to AVP or oCRF by 10(-9) mol SP/l was not potentiated by its combination with either 5 X 10(-10) or 10(-8) mol SRIF/l; the inhibitory effects were merely additive. The results suggest that although SRIF and SP are able to modulate the release of ACTH from the anterior pituitary gland, they do so only at a high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hypothalamic neuropeptides on corticotrophin release from quarters of rat anterior pituitary gland in vitro. 619 17

Peripheral osmo - and bradykinin-sensitive receptors which have been previously localised within the hepatic portal vein area, activate the hypothalamo-neuro-hypophysial system through a neural pathway projecting to the lower thoracic spinal cord. In this paper we attempted to identify the spinal transmitter(s) involved and to answer the question whether osmoreceptors are in fact chemosensitive nociceptors. The portal vein of anesthetised rats was superfused with 0.2 ml of 4% NaCl or 1 microM bradykinin, and hypothalamo-neurohypophysial responses were measured either electrophysiologically or by radioimmunoassay of arginine vasopressin. Responses to bradykinin, but not to hypertonic saline, were abolished in rats pretreated 2 wks previously with capsaicin s.c., and immunocytochemistry for substance P in these animals showed that substance P was strongly depleted both in the dorsal thoracic spinal cord and in the portal vein. The spinal injection of 8 microliter 0.1 mM capsaicin at T8-T9 elicited a pronounced hypothalamo-neurohypophysial response, and diminished reversibly the response to bradykinin superfusion of the portal vein. Spinal capsaicin had no effect on responses to hypertonic saline. Similarly, the spinal (T8-T9) injection of 8 micrograms substance P antagonist, the [D-Pro4, D- Trp7 ,9,10, Val8 ]substance P (4-11), reduced reversibly the responses to bradykinin by about 50% without affecting those to hypertonic saline. The spinal injection of 8 micrograms substance P, at the same site where substance P antagonist was applied, elicited within 4 s a prolonged response (several min). A slightly longer delay between stimulus and neurophysiological response was observed for spinal capsaicin and for bradykinin superfusion. Responses to hypertonic saline superfusion of the portal vein, however, occurred within 1-2 s. The results show that portal vein osmoreceptors are distinct from chemo-sensitive nociceptors, and suggest that substance P may be a spinal mediator for chemo-sensitive portal vein nociceptors. The spinal transmitter for osmosensitive afferents, and the physiological importance of the portal vein area in chemosensation remain to be established.
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PMID:Spinal substance P transmits bradykinin but not osmotic stimuli from hepatic portal vein to hypothalamus in rat. 620 51

Most neuropeptides can now be assayed in human cerebrospinal fluid (CSF). Some, such as beta-endorphin and arginine vasopressin, seem to be secreted directly into CSF. Others may reach CSF from plasma either by passage through the blood-brain barrier or by absorption through the circumventricular organs, which lack a blood-brain barrier. The role of neuropeptides in CSF is still unclear. Thyrotropin-releasing hormone, somatostatin, arginine vasopressin, angiotensin II, substance P, vasoactive intestinal polypeptide, beta-endorphin, gastrin, and cholecystokinin are all present in assayable quantities in human CSF. Their functions in this fluid are liable to be as diverse as their functions elsewhere in the body. The release of hypothalamic releasing factors into the CSF may be part of the pathway of pituitary hormone release. Pituitary hormones may function in CSF as part of a feedback loop from the hypothalamus. Other neuropeptides may affect receptors in the central nervous system far away from their release site. Intraventricular neuropeptide injection, anatomical and physiological ablation experiments, receptor studies, and neurobiological techniques now being developed will allow a more complete understanding of CSF neuropeptide function in the future.
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PMID:Neuropeptides in cerebrospinal fluid. 675 95

Intracerebroventricular (i.c.v.) injections of senktide (0.01-10 nmol), a tachykinin NK-3 agonist, had an antidiuretic action in water-loaded rats (4.5% body wt.). Pretreatment with OPC-31260 (1 mg/kg, i.v.), a non-peptide vasopressin V2 antagonist, inhibited the antidiuretic action induced by exogenous arginine vasopressin (AVP, 0.1 micrograms/kg, i.v.) and senktide (0.1 nmol, i.c.v.). In addition, senktide (11.8 nmol, i.c.v.) caused a marked increase of the plasma AVP level in conscious rats. These results suggest that the central NKB analogue senktide has an antidiuretic effect by stimulating AVP secretion from the pituitary gland through the NK-3 receptor in the hypothalamus.
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PMID:Central administration of senktide, a tachykinin NK-3 agonist, has an antidiuretic action by stimulating AVP release in water-loaded rats. 750 13

In this study, the concentration of plasma arginine vasopressin (AVP) and substance P (SP) in normotensive subjects as well as patients with essential hypertension was measured. The results showed that: (1) The concentration of plasma AVP in patients with essential hypertension (21.83 +/- 1.30ng/L) was significantly higher than that in normotensive subjects (11.02 +/- 1.05 ng/L) (P < 0.001). The level of plasma SP in hypertensive subjects (276.60 +/- 21.35 pmol/L) was obviously lower than that in normotensive subjects (958.20 +/- 31.13 pmol/L) (P < 0.001). (2) The level of plasma AVP decreased (from 24.88 +/- 1.63 to 8.69 +/- 1.39 ng/L, P < 0.001) and that of plasma SP increased (from 331.40 +/- 48.18 to 958.80 +/- 39.30 pmol/L, P < 0.001) after antihypertensive drug treatment. (3) A negative correlation was found between the level of plasma AVP and SP in patients with essential hypertension (r = -0.564, P < 0.001), but no correlation was found between them in normotensive subjects (r = -0.096, P > 0.05). It is suggested that the abnormal level of plasma AVP and SP plays a role in the pathogenesis of hypertension.
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PMID:[The role of arginine-vasopressin and substance P in the pathogenesis of hypertension and their interrelation]. 750 32

Human umbilical vessels are unique in lacking any innervation; thus endothelial cells may play the major role in local control and regulation of the blood flow. In the present study, we examined ultrathin sections of cultured human umbilical vein endothelial cells and tissue preparations of umbilical vein and artery, immunostained by the post-embedding colloidal gold double-labelling technique. We observed colocalization of atrial natriuretic peptide and neuropeptide Y, as well as colocalization of atrial natriuretic peptide and neuropeptide Y with other vasoactive substances, namely, vasoactive intestinal peptide, substance P, calcitonin gene-related peptide and arginine vasopressin. The functional significance of the colocalization of these vasoactive substances in the human umbilical vessel endothelial cells is discussed.
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PMID:Colocalization of vasoactive substances in the endothelial cells of human umbilical vessels. 750 9

The cerebral vasculature of five anaesthetised rabbits was perfused with a perfluorocarbon emulsion via the internal carotid arteries, and the effluent from the jugular veins analysed for ATP, substance P (SP), endothelin (ET) and arginine vasopressin (AVP). Viability of the preparation was monitored periodically by the electrocorticogram, oxygen uptake, carbon dioxide release and perfusion pressure. The basal rate of infusion of 7.8 +/- 1.26 ml.min-1 resulted in an infusion pressure of 114.0 +/- 22.1 mmHg and when increased first to 10.5 +/- 1.53 ml.min-1 and then to 15.0 +/- 1.87 ml.min-1, rose to 163.0 +/- 33.1 mmHg and to 170.0 +/- 33.2 mmHg, respectively. Between each 3-min period of increased flow the rate was returned to the basal rate for 6 min. Of the four vasoactive substances, ET was released at the largest rate during the initial period of basal flow, 65.3 +/- 10.7 pmol.min-1. This increased further when the infusion rate rose to 10.5 ml.min-1, but was significant only when the infusion rate was increased to 15.0 ml.min-1. ATP was released at 41.5 +/- 11.5 pmol.min-1 during the initial period of basal flow. Its release significantly increased with flow and peaked at 15.0 ml.min-1. SP was released at a rate of 13.3 +/- 8.2 pmol.min-1 during the initial period of basal flow. Its rate of release was increased significantly the second time the flow was increased to 10.5 ml.min-1 and increased even further when the flow was increased to 15.0 ml.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of changes in rate of vascular perfusion on release of substances into the effluent from the brain of the rabbit. 750 14

Small cell lung cancers (SCLC) and some non-small cell lung cancers (NSCLC) have neuroendocrine features which include production of a variety of neuropeptides, cell surface expression of the receptors for these peptides, and autocrine stimulation by the peptides. Previous studies showed that some peptide antagonists and anti-peptide antibodies inhibited the growth of SCLC cell lines which expressed receptors for the specific peptide. We and others showed that the heterogeneity of peptide receptor expression and responsiveness was a major potential obstacle for developing therapeutic uses of peptide antagonists. In this manuscript we evaluated the effects of 11 peptide antagonists (3 bombesin-specific, 2 cholecystokinin-specific, 1 arginine vasopressin (AVP)-specific, and 5 substance P derivatives with broad specificity) on peptide-induced calcium mobilization and growth of SCLC and NSCLC cell lines. For each antagonist, we determined the dose-response effects, specificity of peptide antagonism, and biological stability in serum using Indo-1AM-based flow cytometric assays. We found that the three bombesin antagonists, S30, SC196, and L336,175, varied in potency from 10 nM to 10 microM, varied in serum stability from 6 h to more than 24 h, and had no effect on the calcium response elicited by other peptides. None of these compounds effectively inhibited the growth of SCLC cell lines in [3H]dThd and cell growth assays in vitro. Similarly, the three cholecystokinin and AVP antagonists were highly specific for cholecystokinin and AVP, respectively, had widely varying potency, but had little inhibitory effect on SCLC growth in vitro. In contrast, the five substance P derivatives inhibited the calcium response to bombesin, AVP, bradykinin, and fetal bovine serum. None of these five antagonists were as potent as the six specific antagonists described above, but they were more effective in inhibiting the growth of SCLC cell lines in vitro. These substance P derivatives inhibited the growth of peptide-sensitive SCLC cell lines more efficiently than their inhibition of peptide-insensitive NSCLC or breast cancer cell lines. Relatively high concentrations of these substance P derivatives were required to inhibit in vitro growth, even in the absence of added peptide. It is likely that more potent broad spectrum antagonists, toxins, or radiolabeled stable antagonists will need to be developed for maximal clinical development of this type of anti-growth factor therapy.
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PMID:Effects of neuropeptide analogues on calcium flux and proliferation in lung cancer cell lines. 751 22

Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involved, and (3) susceptibility to NG-nitro-L-arginine (L-NA), an NO synthase inhibitor, of the response to mediators liberating NO from the endothelium and nerve differs. Changes in isometric tension were recorded. In the strips contracted with prostaglandin F2 alpha, substance P and arginine vasopressin produced a relaxation which was abolished or reversed to a contraction by endothelium denudation. The relaxations were not influenced by indomethacin but were suppressed dose-dependently by L-NA, as was the response to nicotine that stimulates the non-adrenergic, non-cholinergic vasodilator nerve and liberates NO. The inhibitions were reversed by L- but not D-arginine. NO (acidified NaNO2)-induced relaxations were not reduced by L-NA. The inhibitory effect was greater in the responses to vasopressin than substance P; however, there was no significant difference in the response to nicotine vs. the peptides. Substance P increased the level of cyclic guanosine monophosphate (GMP) in the artery strips with the intact endothelium, the effect being abolished by endothelium denudation, L-NA and oxyhemoglobin. Relaxations caused by adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were dependent partially on the endothelium. Treatment with L-NA attenuated the ATP-induced relaxation in the strips with endothelium but did not alter the response of denuded strips.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebroarterial relaxations mediated by nitric oxide derived from endothelium and vasodilator nerve. 768 37


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