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)

Endothelin-1 is a 21 amino acid peptide originally isolated from porcine aortic endothelium and has recently been localized within the central nervous system. We have administered endothelin-1 in a dynamic perfusion system in order to study its possible effects on the rat hypothalamus and anterior pituitary. Tissue (hypothalami or quartered pituitaries) was placed into plastic chambers and was perfused with oxygenated Krebs-bicarbonate solution. After an interval to establish stable basal peptide release, endothelin-1 was administered at two doses (0.1 and 1 microM) and the release of substance P, vasoactive intestinal peptide, 7B2, and somatostatin was measured, the last being detectable only in hypothalamic perfusates. Both concentrations of endothelin-1 led to a significant increase (P less than 0.01) in the release of substance P from the hypothalamus and pituitary, but not of vasoactive intestinal peptide, 7B2, or somatostatin. Thus after the 0.1 microM and 1 microM endothelin-1 perfusion substance P release from the hypothalamus increased by 125 +/- 5% and 215 +/- 15% (mean +/- SEM) of basal and from the pituitary by 168 +/- 8% and 276 +/- 15% (mean +/- SEM). No change occurred in the output of ACTH or other pituitary hormones. The release of substance P from hypothalamus or pituitary after stimulation with endothelin-1 was not blocked when a calcium free medium was used. Endothelin-1 binding sites were identified on rat pituitary cell membranes. These findings suggest the possibility that endothelin may act as a paracrine substance, neurotransmitter, or neuromodulator in the hypothalamo-pituitary axis.
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PMID:Release of substance P from rat hypothalamus and pituitary by endothelin. 169 95

Bacterial lipopolysaccharide (LPS) and corticotropin releasing hormone (CRH) plus arginine vasopressin (AVP) induce immunoassayable (1-13)ACTH (alpha MSH) from mononuclear leukocytes. We studied the ability of LPS and CRH + AVP to in vitro stimulate native ACTH (not alpha MSH) and substance P (SP) production and thymidine incorporation in human mononuclear leukocytes. Neither CRH + AVP nor LPS stimulated detectable amounts of intracellular or extracellular ACTH (less than 15 pg/8 x 10(6) cells or total medium) or SP (less than 50 pg/8 x 10(6) cells or total medium) at 1, 2, 3 or 4 days of incubation. LPS, but not CRF + AVP, increased the amount of 3H-thymidine incorporation over controls. This data questions the importance of an immunoadrenal axis and the synthesis of SP by mononuclear leukocytes.
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PMID:Corticotropin releasing hormone and arginine vasopressin stimulation of ACTH and substance P in human mononuclear leukocytes. 169 18

We have investigated the central effects of substance P (SP) on plasma concentrations of immunoreactive ACTH and on immunoreactive and bioactive arginine vasopressin (AVP) in the rat. The injection of SP (20 nmol) into the lateral ventricle intracerebroventricular, (i.c.v.) of ethanol-anaesthetised rats produced a prolonged antidiuresis lasting at least 30 min, associated with an increase in plasma AVP (from 7.8 +/- 0.6 to 12.5 +/- 1.9 fmol/ml, mean +/- SEM, n = 6). Concentrations of plasma ACTH were significantly decreased 30 min following SP (from 320 +/- 70 to 135 +/- 15 fmol/ml, n = 12). In rats anaesthetised with urethane, a significant decrease in plasma ACTH was observed 15 and 30 min following i.c.v. injection of SP (20 nmol); a downward trend was also observed in ACTH following a 40 nmol dose, but this was not significant. No effect of SP was observed on either basal or CRF-41-stimulated ACTH release from isolated rat anterior pituitary cells in vitro. These results demonstrate for the first time that SP exerts opposite effects upon the release of ACTH and AVP in the same animal, and suggest that these actions occur at the level of the hypothalamus.
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PMID:Substance P stimulates arginine vasopressin and inhibits adrenocorticotropin release in vivo in the rat. 169 61

We have used specific radioimmunoassays coupled with reversed-phase high-performance liquid chromatography (HPLC) to measure and characterise substance P (SP) and substance K (SK) in subdivisions of the rat hypothalamus. SP and SK levels in the paraventricular nucleus (PVN) were 968 +/- 61 and 381 +/- 22 pg respectively; in the supraoptic nucleus (SON) were 210 +/- 21 and 79 +/- 8 pg; and in the median eminence/arcuate nucleus (ME) were 1044 +/- 66 and 451 +/- 20 pg. Reversed-phase HPLC revealed that immunoreactive (ir) SP was present solely in the non-oxidised form in all tissue extracts. The principal form of ir-SK in the PVN and SON coeluted with synthetic SK on HPLC, but some immunoreactivity eluted in a later position. This material represented less then 5% of the total ir-SK in extracts of the PVN and SON, but increased to 35-40% of the total in the ME. Gel chromatography and HPLC characterised this compound as being slightly smaller and more hydrophobic than SK. These results establish that ir-SK is present within the hypothalamus in varying amounts and molecular forms. The location of significant amounts of both SP and SK in the PVN and ME, the principal regions of CRF-41 synthesis and release, is compatible with a role for neurokinins in the modulation of CRF-41 and consequently ACTH release.
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PMID:Substance P and substance K in the median eminence and paraventricular nucleus of the rat hypothalamus. 170 3

These findings suggest that SP may have proinflammatory actions in both the peripheral tissue and the central nervous system after tissue injury. Although the possibility that the same neuropeptide could have actions in both the brain and the peripheral tissues is certainly not without precedent, there is a key difference in the source of the ligand in these tissues. Unlike peripheral tissues such as the gastrointestinal tract or skin, where there is a dense innervation by SP-containing dorsal root ganglion neurons, the brain lacks such a sensory innervation. This important difference raises the question as to the possible origin of the SP that could occupy the SP receptors expressed by the CNS glia after neuronal injury. Whereas the answer to this question is currently unknown, an important clue may be the findings that circulating leukocytes have been reported to synthesize neuropeptides such as ACTH, opiates, and SP. To begin to fully understand the role that SP may play in coordinating the inflammatory and immune response to tissue injury, we must first understand where SP fits into the cascade of events that occur after tissue injury, what events lead to nociceptor sensitization (which may lead to an increase in SP release), and what regulates SP receptor expression (which may be involved in the direction of leukocytes to the site of injury, plasma extravasation, or the proliferation/hypertrophy of reactive astrocytes). Although this may seem like a daunting task, several recent advances including the cloning of the three mammalian tachykinin receptors and the introduction of highly potent and specific SP receptor antagonists should make this a highly fruitful field of investigation.
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PMID:Substance P and the inflammatory and immune response. 171 71

22 gastric carcinomas (13 intestinal type and nine diffuse type) were immunostained for neuron specific enolase, chromogranin, Leu-7 and a panel of fifteen different peptide hormones. Five out of the 13 tumours of intestinal type and four out of the nine diffuse carcinomas expressed immunoreactivity for one or more of the pan endocrine markers. Seven out of the 13 tumours of intestinal type and five out of the nine diffuse carcinomas also expressed immunoreactivity for gastrin (3), ACTH (3), serotonin (7) and calcitonin (7). Immunoreactivity for somatostatin (1) and substance P (1) were also seen in two tumours of intestinal type. Seven out of 18 cases with benign mucosa adjacent to the tumours expressed a focal immunoreactivity for chromogranin (6), serotonin (6), gastrin (5) and calcitonin (1). All hormone-producing tumours also expressed immunoreactivity for carcino-embryonic antigen. Our results confirm that a high proportion of gastric carcinomas are hormone producing.
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PMID:Endocrine profile in gastric carcinomas. An immunohistochemical study. 172 59

1. Corticotropin-stimulated lipolysis in adipocytes of rats, mice, hamsters, guinea pigs and rabbits. Melanotropins elicited high lipolytic activity only in guinea pig and rabbit adipocytes. Opiate peptides were active only in rabbit adipocytes. Pituitary and chorionic gonadotropins and somatotropin were lipolytic in guinea pig adipocytes. Other hormones tested including prolactin, somatostatin, substance P, neurotensin, angiotensin II, thyrotropin releasing hormone and pancreatic polypeptide were devoid of lipolytic activity in all of the adipocytes studied. 2. In the rabbit adipocytes gamma-melanotropin was lipolytic only at high doses. At these doses the peptide inhibited the lipolytic response to a high dose of corticotropin. 3. Lipolysis stimulated by vasoactive intestinal peptide and epinephrine in rat adipocytes was antagonized by insulin. The lipolytic hormones corticotropin, epinephrine, vasoactive intestinal peptide and secretin suppressed basal and insulin-stimulated lipogenesis.
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PMID:Studies on hormonal regulation of lipolysis and lipogenesis in fat cells of various mammalian species. 196 44

The specific melanotropin (MSH) binding sites of rat lacrimal glands were characterized with respect to anatomic distribution, peptide specificity and selectivity, and coupling to a biological response. Tissue distribution of MSH binding sites was determined by autoradiography following in situ binding of a radiolabeled, biologically active preparation of a superpotent alpha-MSH analog, [125I]-[Nle4,D-Phe7]-alpha-MSH ([125I]-NDP-MSH). Intense, specific (i.e., alpha-MSH-displaceable) [125I]-NDP-MSH binding was observed throughout lacrimal acinar tissue, but not in ducts or stroma. In freshly isolated lacrimal acinar cells, specific binding of [125I]-NDP-MSH was maximal within 30 min and rapidly reversible, with a dissociation half-time of about 15 min. A number of melanotropins [alpha-MSH, [N,O-diacetyl-Ser1]-alpha-MSH, [des-acetyl-Ser1]-alpha-MSH, beta-MSH, ACTH(1-24) and ACTH(1-39)] were recognized by these binding sites, as assessed by their inhibition of [125I]-NDP-MSH binding; NDP-MSH was the most potent (IC50 = 1.3 x 10(-9) M). In contrast, other peptides, including ACTH(4-10) and the nonmelanotropic peptides VIP, substance P, somatostatin, and ACTH(18-39) (CLIP), had no effects on tracer binding. In isolated lacrimal acinar cells, alpha-MSH and NDP-MSH stimulated intracellular cyclic AMP accumulation. We conclude that lacrimal acinar cells express functional receptors recognizing melanotropins, suggesting that the lacrimal gland may be a target for physiological regulation by endogenous melanotropins.
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PMID:Characterization of functional melanotropin receptors in lacrimal glands of the rat. 216 77

We have investigated the appearance of the transmitter phenotypes of hypothalamic neurons in grafts transplanted into the third ventricle of adult female rats. The grafts were the mediobasal hypothalamus and the preoptic area of 12.5-day-old rat embryos, and were examined 40-100 days later. Wheat germ agglutinin (WGA) was injected into the jugular vein of several animals for the examination of the existence of neurovascular associations. Three days after the injection, WGA appeared to have been incorporated into the neurons in the paraventricular, periventricular, and arcuate nuclei of the host animals. In the grafts, WGA was also seen incorporated in certain neurons which were found immunoreactive for tyrosine hydroxylase (TH), rat corticotropin-releasing factor (rCRF), substance P (SP), or somatostatin (SRIH). Neurons immunoreactive for neuropeptide Y (NPY) and ACTH did not seem to incorporate WGA. These findings suggest that the neurons containing TH, rCRF, SP, or SRIH link with fenestrated capillaries developed in the grafts. The immunoreactivity for glucocorticoid receptor (GR) was detected mainly in the nucleus of certain neurons and glial cells in the grafts as well as in the host hypothalamic neurons. In the grafts, strong GR immunoreactivity was detected in the cells immunoreactive for TH, NPY, and rCRF as in the host animals. It is concluded that the undifferentiated hypothalamic neurons differentiate to synthesize GR as well as definitive peptides and TH in the grafts.
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PMID:Appearance of neurons with glucocorticoid receptors and neurovascular links in the embryonal rat hypothalamus grafted in the third ventricle. 229 64

Although some cultured human melanoma cell lines are responsive to melanotropins (melanocyte-stimulating hormones [MSH]), the prevalence and tissue distribution of MSH receptors in melanoma are unknown. We report here the use of an in situ binding technique to demonstrate specific MSH receptors in surgical specimens of human melanoma. The distribution and binding properties of specific MSH binding sites were determined by autoradiography and image analysis after incubation of frozen tumor tissue sections with a biologically active, radiolabeled analogue of alpha-MSH, [125I]iodo-Nle4, D-Phe7-alpha-MSH ([125I]NDP-MSH). In melanoma specimens from 11 patients, 3 showed high levels of specific binding, 5 showed low levels, and in 3 patients specific binding of [125I]NDP-MSH was not detectable. Specific MSH binding sites were present in melanoma cells, but not in adjacent connective or inflammatory tissues. Melanotropins, including alpha-MSH, NDP-MSH, and ACTH, inhibited [125I]NDP-MSH binding in a concentration-dependent manner, whereas unrelated peptides (somatostatin and substance P) did not. The apparent affinity of alpha-MSH for this binding site was in the nanomolar range (EC50 = 2 X 10(-9) M for inhibition of [125I]NDP-MSH binding in situ), similar to that recently described for the murine melanoma receptor. In one patient, analysis of multiple intratumor samples and tumors excised on three separate occasions revealed high levels of specific MSH binding in all samples. These results suggest that endogenous melanotropins may modulate the activities of human melanoma cells in vivo.
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PMID:Melanotropin receptors demonstrated in situ in human melanoma. 234 15


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