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

A major advance in transport physiology was H. H. Ussing's development of the voltage-clamp method, and later the Koefoed-Johnsen-Ussing model for Na+ transport. In the same decade, J. C. Skou identified the Na(+)-K(+)-ATPase, which maintains the Na+ and K+ gradients that drive most epithelial transport processes. With this foundation, Danish scientists have pursued the mechanism of ion transport and the resulting solute-linked water flow. Recent contributions have been on isosmotic transport, suggesting solute recycling, and KCl-water cotransport in the basolateral epithelial cell membrane. Efficient small intestinal nutrient absorption is dependent on coupling to the Na+ gradient. Cotransport of Na+ and glucose is quantitatively the most important absorptive mechanism in the small intestine, as illustrated by the success of oral rehydration solutions in diarrhoea. The majority of amino acids are likewise transported by Na+ dependent carriers, but recent experiments have identified a concomitant Cl- dependency for some. Regulation of intestinal secretion, both under normal digestive processes, and in response to enterotoxins, has turned out to be very complex. It involves local and central neuronal regulation through an array of neurotransmitters and local actions of gastrointestinal hormones. Major effectors are the submucosal neurons and the main transmitters serotonin, vasoactive intestinal peptide, acetylcholine, substance P, and neurotensin. Development of antisecretagogues is impeded by the existence of several receptor subtypes and significant species differences. The Na+ and water-conserving properties of the large intestine have been shown to be regulated by adrenocortical hormones, with aldosterone as a potent stimulator of colonic Na+ absorption. A major colonic function is the symbiosis with the anaerobic bacterial population. The fermentation of carbohydrate to short-chain fatty acids, which can be absorbed, supplements small intestinal digestive function.
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PMID:Experimental studies of intestinal ion and water transport. 872 83

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

The role played by endogenous substance P (SP) in the regulation of hypothalamo-pituitary-adrenal (HPA) axis was investigated in the rat. Normal and ether-stressed (2 min ether-vapor inhalation) or cold-stressed (20 min at 4 degrees C) animals were given a bolus subcutaneous injection of 100 nmol spantide (SPA) a specific antagonist of SP; their blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA, 1, 2 or 4 h after the injection. SPA did not evoke significant changes in the basal plasma levels of the three hormones. Ether and cold stresses markedly raised the blood concentrations of ACTH, ALDO and B, being maximal response observed after 1 or 2 h. SPA notably enhanced the responses of the three hormones to ether stress. SPA magnified ALDO and B responses to cold stress, but it notably depressed ACTH one. In light of these findings, it may be concluded that (i) endogenous SP does not affect basal activity of rat HPA axis, but it exerts an inhibitory action on its response to the stresses, especially the ether-inhalation one: and (ii) different mechanisms are involved in the cold and ether stress-induced activation of the HPA axis.
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PMID:The possible role of endogenous substance P in the modulation of the response of rat pituitary-adrenal axis to stresses. 887 42

In this work, we have studied the effects and the possible cellular mechanism of Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele crested newt, Triturus carnifex. Adrenals were in vitro superfused with SP, prostaglandin E2 (PGE2), nitric oxide (NO) donor, cyclic GMP (cGMP) analogue, and inhibitors of phospholipase A1, phospholipase A2 (PLA2), phospholipase C, adenylate cyclase (AC), cyclooxygenase (COX), NO synthase (NOS), and soluble guanylate cyclase (sGC). PGE2, corticosterone, and aldosterone release and NOS activity were determined. SP, PGE2, NO donor, and cGMP analogue increased corticosterone and aldosterone; SP and PGE2 increased NOS, and SP increased PGE2. PLA2, AC, COX, NOS, and sGC inhibitors counteracted SP and PGE2 effects, except for PLA2, which did not affect PGE2. These results suggest that SP exhibits a stimulatory role on the corticosteroidogenesis of T. carnifex adrenal gland. In particular SP enhances PLA2 activity, increasing PGE2; this prostaglandin affects AC, which, in turn, enhances NO, and the latter therefore affects sGC, with the consequent corticosteroidogenesis increase.
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PMID:Cellular mechanism of substance P in the regulation of corticosteroid secretion by newt adrenal gland. 914 46

Substance P (SP) did not affect either basal or agonist-stimulated aldosterone production by dispersed rat zona glomerulosa (ZG) cells. In contrast, the SP-receptor antagonist spantide-II (SPA), at 10(-8)/10(-6) M concentrations, markedly raised basal and 10(-9) M ACTH, but not 10(-9) M angiotensin II-stimulated aldosterone secretion. The secretagogue effect of 10(-6) M SPA was annulled by SP (10(-6) M) and the protein kinase (PK)-C inhibitor Ro31-8220 (10(-6) M), but was unaffected by the PKA inhibitor H-89 (10(-5) M). In light of these findings the following conclusions can be drawn: (i) SP does not exert a physiologically relevant direct modulatory action on aldosterone secretion of rat ZG cells; (ii) a receptor-independent inhibitory interaction is likely to occur between SP and SPA molecules; and (iii) SPA activates, through a receptor-independent mechanism, phosphoinositide signaling pathway in rat ZG cells.
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PMID:Stimulatory effect of the substance P antagonist spantide-II on aldosterone secretion of dispersed rat zona glomerulosa cells. 918 44

We have previously shown that the frog adrenal gland is innervated by a dense network of fibers containing ranakinin, one of the endogenous tachykinins in the amphibian Rana ridibunda, and we have found that ranakinin stimulates in vitro corticosteroid secretion by frog adrenal tissue. To elucidate the mechanism of action of ranakinin on the frog adrenal gland, we investigated the effect of ranakinin on cAMP formation and polyphosphoinositide metabolism. Incubation of frog adrenal explants with various tachykinins, including ranakinin, substance P, neurokinin A, or neurokinin B, did not produce any significant modification of cAMP concentrations. In contrast, ranakinin induced a time- and dose-dependent stimulation of inositol phosphate formation with a concomitant decrease in membrane polyphosphoinositides. Pretreatment of the tissue slices with the phospholipase C inhibitor U-73122 or with pertussis toxin completely abolished the stimulatory effect of ranakinin on inositol phosphate formation. Prolonged administration of U-73122 to perifused frog adrenal explants markedly attenuated the ranakinin-evoked stimulation of corticosterone and aldosterone secretion. Taken together, these data indicate that in the frog adrenal gland, ranakinin has no effect on the adenylyl cyclase system, but enhances polyphosphoinositide hydrolysis. The stimulatory action of ranakinin on inositol phosphate formation and corticosteroid secretion is mediated through activation of a phospholipase C positively coupled to a pertussis toxin-sensitive G protein.
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PMID:Ranakinin, a naturally occurring tachykinin, stimulates phospholipase C activity in the frog adrenal gland. 944 18

Tachykinins are a family of neuropeptides, which act by binding to three main subtypes of G protein-coupled receptors, named NK1, NK2 and NK3. Tachykinins are contained in both nerve fibers and secretory cells of the hypothalamo-pituitary-adrenal (HPA) axis, and evidence indicates that they take part in the functional control of it. Tachykinins involved in this function include substance P (SP), neuropeptide K and its derivative neurokinin A (NKA), and neurokinin B, which preferentially bind to NK1, NK2 and NK3 receptors, respectively. NK1 agonists exert an inhibitory effect on the hypothalamo pituitary CRH/ACTH system, while NK2 and perhaps NK3 agonists stimulate it, thereby controlling the secretion and growth of the adrenal cortex via circulating ACTH. Intra-adrenal tachykinins may also affect the cortex function. Their direct action on adrenocortical cells is doubtful and probably pharmacologic in nature, but several investigations suggest that tachykinins indirectly stimulate the cortex by acting on medullary chromaffin cells, which in turn exert a paracrine control on adrenocortical cells. SP enhances aldosterone production of zona glomerulosa by eliciting catecholamine secretion; neuropeptide K and NKA raise glucocorticoid production of zonae fasciculata and reticularis through the activation of the intramedullary CRH/ACTH system. The relevance of these effects of tachykinins under basal conditions is questionable, although there are indications that SP is involved in the maintenance of a normal growth and steroidogenic capacity of rat zona glomerulosa, and that SP and NKA play an important role in the stimulation of the adrenal growth during the fetal life. In contrast, evidence has been provided that the role of tachykinins, and especially of SP, could become very relevant under paraphysiological (e.g., physical or inflammatory stresses) or pathological conditions (e.g., ACTH-secreting pituitary tumors), when an excess of steroid-hormone production has to be counteracted.
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PMID:Role of tachykinins in the regulation of the hypothalamo-pituitary-adrenal axis. 966 62

Activation of the renin-angiotensin-aldosterone system (RAAS) in left ventricular systolic dysfunction is a critically important determinant in the pathophysiologic processes that lead to progression of heart failure and sudden death. Angiotensin II, acting at the specific angiotensin receptor (AT1-R), activates a series of intracellular signaling sequences which are ultimately expressed within the cardiovascular system as vasoconstriction and associated vascular hypertrophy and remodeling. Angiotensin converting enzyme (ACE) inhibition leads to increases in the vasodilatory peptides bradykinin and substance P and at least an initial reduction in angiotensin II concentrations. AT1-R blocking drugs prevent access of angiotensin II to the AT1-R and thus prevent cellular activation. ACE inhibitors have clearly been demonstrated through a large number of clinical trials to increase survival in congestive heart failure, primarily by reducing the rate of progression of left ventricular dilatation and decompensation. However, this beneficial effect diminishes over time. Preliminary short-term clinical studies evaluating the efficacy of AT1-R blocking drugs in the treatment of heart failure have suggested that they elicit similar hemodynamic and neuroendocrine effects as do the ACE inhibitors. The combination ACE inhibitors and AT1-R blocking drugs offer the theoretical advantage of increasing bradykinin while blocking the actions of angiotensin II, and thus possibly show a synergistic effect. Again, preliminary studies have yielded encouraging results that are difficult to interpret because neither ACE inhibitor nor the AT1-R blocking drug doses were titrated to tolerance. Pharmacological manipulation of the RAAS has led to better understanding of its role in heart failure and improved clinical outcomes.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of heart failure caused by left ventricular systolic dysfunction. 1036 49

Adrenocortical steroidogenesis is regulated in addition to a central regulation via the hypothalamus-pituitary-adrenal axis by intra-adrenal mechanisms involving the adrenal medulla. We could previously show that adrenocortical steroidogenesis is stimulated by co-culturing bovine adrenocortical cells with medullary chromaffin cells. This stimulation was due to soluble factors released from the chromaffin cells under basal, unstimulated conditions and involved the increased expression of P450 enzymes, StAR and de novo protein synthesis. In the present study we analyzed the differential regulation of the three cortical zones and characterized secretagogues involved in this stimulation. While cortisol and androstenedione release were increased 10 fold by incubation with chromaffin cell-conditioned medium, aldosterone secretion was not influenced. 80% of the stimulation proved to be due to adrenomedullary epinephrine, norepinephrine, ACTH, PACAP and PG-dependent mechanisms. Other adrenomedullary secretory products, serotonin, Met-enkephalin, Leu-enkephalin, galanin, CGRP, substance P, VIP or NPY did not stimulate steroidogenesis in this system. Our data show that adrenomedullary cells differentially regulate the three adrenocortical zones. This stimulation predominantly depended on epinephrine, norepinephrine, PACAP, and ACTH released from the chromaffin cells and prostaglandin-dependent mechanisms such as interleukin-1.
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PMID:Neurotransmitters and neuropeptides in the differential regulation of steroidogenesis in adrenocortical-chromaffin co-cultures. 1119 60

Tachykinins are a family of neuropeptides that inhibit salt appetite. Although decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats, no decrease is seen in natriorexic sodium-replete rats that are administered the aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis of tachykinins could not account for increased appetite, we hypothesized that increased salt appetite was due to a downregulation of tachykinin receptors. Thus, we injected rats with DOCA once daily for 11 days and analyzed tachykinin receptor subtype, neurokinin 3 (NK3r)-immunoreactivity by Western blot analysis since intracerebroventricular injection of senktide (NK3r agonist) attenuates salt intake in DOCA-treated animals. We examined NK3r-immunoreactivity in several brain regions thought to be associated with the control of water and electrolyte balance including the bed nucleus of the stria terminalis, central nucleus of the amygdala, diagonal band of Broca, hippocampus, nucleus tractus solitarius, parabrachial nucleus, paraventricular nucleus of the hypothalamus, and supraoptic nucleus. Consistent with our hypothesis, we found decreased NK3r-immunoreactivity in all brain regions analyzed except for increases in the amygdala and no changes in the paraventricular nucleus of the hypothalamus. To examine whether DOCA's effects on NK3r synthesis are direct, we used differentiated N1E-115 neuroblastoma cells that express NK3r and treated them with a range of concentrations of DOCA and found a dose-dependent decrease in NK3r-mRNA abundance via Northern blotting. The present results suggest that the tachykinin receptors are downregulated after subchronic DOCA treatment and this finding is consistent with the hypothesis that suppressed inhibition of salt appetite as mediated through the tachykininergic system.
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PMID:Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat. 1250 79


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