UNIPROT:P20366 - FACTA Search

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

When primary cultured bovine adrenocortical cells were treated with substance P (SP) at concentrations higher than 10 pM, cortisol output increased in a dose-dependent fashion. Although other neurokinins, such as neurokinin A (NKA) and neurokinin B (NKB), were also effective in secreting cortisol, SP was the most potent among the tested neurokinins, the potency order being SP greater than NKA much greater than NKB. This suggests that the NK-1 type receptor on adrenocortical cells may be the site of action of SP on cortisol secretion. The maximal response in SP-induced cortisol secretion was comparable to that elicited by adrenocorticotropic hormone (ACTH). SP-induced cortisol secretion was dependent upon extracellular Ca2+ concentrations, and 45Ca2+ uptake into adrenocortical cells treated with SP was long-lasting. While, in the case of ACTH, 45Ca2+ uptake proceeded transiently, the increase in intracellular cAMP content was much greater compared with that of SP. Although KT-5720, an inhibitor of protein kinase A, inhibited potently ACTH-induced cortisol secretion, SP-induced secretin was not affected by this inhibitor at all. On the other hand, calmodulin inhibitors, such as calmidazolium, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, were not more effective in inhibiting SP-induced cortisol secretion than secretion induced by ACTH. The present study indicates that SP may be one of the physiological stimulants of cortisol secretion and that an increase in intracellular Ca2+ concentration and the subsequent activation of calmodulin may precede SP-induced cortisol secretion.
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PMID:Cortisol secretion induced by substance P from bovine adrenocortical cells and its inhibition by calmodulin inhibitors. 137 83

In order to clarify the mechanism of substance P (SP)-induced cortisol secretion from bovine adrenocortical (BAC) cells, protein synthesis at the early stage of SP-stimulation in BAC cells was investigated. Both SP and adrenocorticotropic hormone (ACTH) increased [3H]leucine uptake into BAC cells in a dose-dependent fashion. Although the SP-induced [3H]leucine uptake precedes the cortisol secretion, ACTH was slower in inducing [3H]leucine uptake and cortisol secretion. Protein synthesis inhibitors, actinomycin D and cycloheximide, were potent in inhibiting the SP-induced cortisol secretion. SDS-PAGE analysis, revealed that a 240 kDa protein is newly synthesized in BAC cells in response to SP but not ACTH. It was also indicated that the production of this 240 kDa protein was elicited about 30 min after stimulation by SP. Moreover, A23187 and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also caused a rapid [3H]leucine uptake and production of 240 kDa protein. In contrast, dibutyryl cAMP did not induce the synthesis of this 240 kDa protein. Calmidazolium, a calmodulin inhibitor, effectively inhibited not only [3H]leucine uptake but also 240 kDa protein production due to SP. On the other hand, KT-5720, an inhibitor of protein kinase A, had no effect on [3H]leucine uptake or 240 kDa production. Using the [125I]calmodulin-membrane overlay method, it was found that the 240 kDa protein was a newly synthesized calmodulin binding protein. From the present study, it was concluded that the de novo synthesis of this 240 kDa protein may be intimately related to the cortisol secretion in SP-stimulated BAC cells associated with an activation of the Ca-calmodulin pathway.
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PMID:de novo synthesis of calmodulin binding protein in substance P-induced steroidogenesis in bovine adrenocortical cells. 138

The hypophysis of the lizard Gallotia galloti showed substance-P-like immunoreactivity in both the adenohypophysis (pars distalis, PD; pars intermedia, PI) and the neurohypophysis (median eminence and pars nervosa), whereas angiotensin-II-like immunoreactivity appeared only in PD and PI. The elution-restaining procedure has allowed us to demonstrate the colocalization of both peptides with adrenocorticotropic hormone (ACTH) in PD and PI cells. Electron microscopic study revealed the presence of substance P immunoreactivity on ACTH secretory granules. The ontogeny of both peptides in corticotropic cells has been studied, revealing that the presence of substance P in ACTH-containing cells of the PI occurs from the embryonic stage 33 (S 33), whereas in the PD it occurs from S 34, coinciding with the appearance of ACTH within the same cells. In both median eminence and pars nervosa of the neurohypophysis, substance P appeared later in development, at S 38. Angiotensin II immunoreactivity in PI cells first appeared at S 38, while in PD it appeared from S 40.
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PMID:Presence of substance P and angiotensin II in corticotropic cells of the lizard Gallotia galloti: immunochemical study in the adult and during ontogenesis. 171 56

The presence of adrenocorticotropic hormone (ACTH) and substance P (SP) receptors on leukocytes is suggestive that these cells can respond to these ligands. To address this possibility, we have investigated the consequences of ACTH and SP stimulation of B cells. As a result, enhanced immunoglobulin synthesis mimicking an IL-4-like mechanism was noted. Importantly, this stimulation could be induced at ligand concentrations at or near the kD for their receptors. Herein these effects by ACTH and SP were described using B cell lymphoma cell lines and normal B cells.
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PMID:The regulation of antibody responses by mini-cytokines. 172 64

An immunocytochemical analysis with 33 antisera was undertaken to investigate the localization of 25 different neurotransmitter-related antigens in the hypothalamic suprachiasmatic nucleus in the rat. To obtain estimates of relative densities of immunoreactive axons a stereological approach was used involving counting of intersections of immunoreactive axons with a superimposed semi-circle test grid. All neurotransmitter-related antigens found in perikarya within the suprachiasmatic nucleus, including those stained with antisera against bombesin, gastrin-releasing peptide, neurophysin, vasopressin, somatostatin, gamma-aminobutyrate, glutamate decarboxylase and vasoactive intestinal polypeptide were also found in axons within the nucleus. A greater number of these immunoreactive axons was found within the nucleus than in the adjacent anterior hypothalamus. The size of all immunoreactive axons in the suprachiasmatic nucleus was consistently small; immunoreactive axons were found ramifying widely in the nucleus, often ending with terminal boutons near perikarya immunoreactive for the same antigen. All neurotransmitter-related substances found in perikarya of the suprachiasmatic nucleus were also found in axons crossing over the midline to innervate the contralateral nucleus, providing an anatomical substrate for a high degree of communication between the paired nuclei. Axons immunoreactive for other putative transmitters including serotonin arising outside the nucleus were also found in high densities within the nucleus and crossing over the midline between the nuclei. Immunoreactivity for some transmitters was found in axons of similar densities within and outside the nucleus, including antisera against tyrosine hydroxylase; a small number of dopamine beta-hydroxylase and a few phenylethanolamine N-methyltransferase-immunoreactive axons were found in the SCN, suggesting that dopamine, norepinephrine and epinephrine may occur in a limited number of axons in the nucleus. Small numbers of axons immunoreactive with antisera raised against cholecystokinin, prolactin, substance P, thyrotropin-releasing hormone and choline acetyltransferase were found within the suprachiasmatic nucleus. Axons immunoreactive for luteinizing hormone-releasing hormone, adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone and neurotensin were rarely found within the suprachiasmatic nucleus; axons immunoreactive for luteinizing hormone-releasing hormone, adrenocorticotropic hormone, cholecystokinin and tyrosine hydroxylase were found in both horizontal and coronal sections in the area between the left and right suprachiasmatic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitters of the hypothalamic suprachiasmatic nucleus: immunocytochemical analysis of 25 neuronal antigens. 241 88

The medial preoptic nucleus (MPN) is a sexually dimorphic complex with three major subdivisions. The cell-dense central (MPNc) and medial (MPNm) subdivisions are larger in male rats, while the cell-sparse lateral subdivision (MPNl) occupies a majority of the nucleus in females. In the present study we evaluated the distribution of possible monoaminergic and peptidergic cells and fibers within the MPN, as well as in adjacent regions of the medial preoptic area of the adult male rat. For this, we used an indirect immunohistochemical method with antisera to serotonin (5HT), dopamine beta-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT), corticotropin-releasing factor (CRF), luteotropin-releasing hormone (LRH), somatostatin (SS), thyrotropin-releasing hormone (TRH), oxytocin (OXY), vasopressin (VAS), adrenocorticotropic hormone (1-24; ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), leucine-enkephalin (L-ENK), and calcitonin gene-related peptide (CGRP). The results suggest that cell bodies and/or fibers crossreacting with all of these putative neurotransmitters are differentially distributed within the MPN. Within the MPNm, the densest plexuses of fibers were stained with antisera to SP and NPY, while moderate densities of fibers were stained with anti-DBH, SS, CCK, CGRP, ACTH, and alpha-MSH, and only a few fibers were stained with anti-5HT, TH, NT, VAS, and L-ENK. Moderate numbers of SP- and L-ENK-immunoreactive cell bodies, and a few SS-, NT-, CRF-, and TRH-stained cell bodies were also found within the MPNm. The MPNc contained a dense plexus of CCK-immunoreactive fibers, as well as a few CRF-immunoreactive fibers. Both fiber types were localized almost exclusively to this subdivision, while most of the others studied here appeared to avoid it selectively. This suggests that there are relatively few inputs to the MPNc, and that they tend to avoid other parts of the nucleus, although moderate densities of DBH- and NPY-immunoreactive fibers were found in both the MPNm and MPNc. The MPNc contained several CCK-immunoreactive cell bodies as well as a moderate number of TRH-stained cell bodies. Both cell types were nearly completely localized to the MPNc. The major inputs to the MPNl studied here appear to be stained with antisera to 5HT and L-ENK, although moderate numbers of NT- and CRF- immunoreactive fibers were also found in this part of the nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitter specificity of cells and fibers in the medial preoptic nucleus: an immunohistochemical study in the rat. 242 28

Production and secretion of neuroendocrine peptides by small cell lung cancer (SCLC) has been detected in the past years. Most recently the role of bombesin as an autocrine/paracrine growth modifier has been demonstrated. We used the soft agarose clonogenic assay to evaluate the influence of other neuroendocrine peptides on the in vitro proliferation of SCLC cell lines. Neuroendocrine peptides tested were adrenocorticotropic hormone, arginine vasopressin, calcitonin, glucagon, kassinin, neurotensin, physalaemin, somatostatin, and substance P. Experiments were carried out in serum-free and serum-supplemented media with and without serum-free incubation periods. Our results indicated that the amphibian undecapeptide physalaemin inhibits the clonal and mass culture growth of SCLC cell lines at picomolar concentrations. All other neuroendocrine peptides failed to influence SCLC growth in the test systems used. These results suggest a growth regulating effect of physalaemin and a potential new form of neuroendocrine peptide therapy for SCLC.
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PMID:In vitro growth inhibition of human small cell lung cancer by physalaemin. 243 62

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization. 245 61

In our previous studies substance P-immunoreactive nerve fibers have been demonstrated in the pars distalis of the anterior pituitary in macaque monkeys, and they have been found to contact somatotropes. The present study investigated the relationship of the substance P-immunoreactive fibers to thyrotropes and corticotropes. Macaca mulatta monkeys were used. Sections of the anterior pituitaries were double immunostained with antisera against either substance P and human thyrotropin or substance P and human adrenocorticotropic hormone. Substance P-immunoreactive varicosities were found to be in close proximity to thyrotropes and corticotropes. It is therefore suggested that a direct neural factor may take part in the regulation of thyrotropin and adrenocorticotropic hormone secretion.
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PMID:The relationship of substance P-immunoreactive nerve fibers to thyrotropes and corticotropes in the pars distalis of the anterior pituitary in the monkey. 247 84

Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat. 276 Jun 6

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