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)

Neurokinin A (NKA), which selectively inhibits only cellular dehydration (CD)-induced drinking in adult rats, exerts a more general antidipsogenic effect in pups in which it also inhibits drinking induced by angiotensin II (AII) or suckling deprivation (SD). The inhibition of drinking is precocious (1st-3rd day) and never involves the intake of milk. The inhibition of CD-induced drinking increases with age, while that of AII- or SD-induced drinking progressively decreases and disappears on day 12-15. In the rat, NKA is therefore a precocious and selective inhibitor of drinking behavior and its selectivity is achieved ontogenetically.
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PMID:Neurokinin A is a specific and precocious inhibitor of water intake in neonatal rats. 216 34

This study investigated the sensitivity of spontaneously hypertensive rats (SHR) and of Wistar Kyoto rats (WKR) to the antidipsogenic action of the tachykinin eledoisin (ELE). Drinking was evoked by: (a) intracerebroventricular (i.c.v.) injection of angiotensin II, (b) subcutaneous (s.c.) administration of hypertonic NaCl (1.5 M; 1 ml/100 g b.wt.) or (c) 18 h of water deprivation with free access to food. In accordance with previous studies, the dipsogenic effect of all three treatments was exaggerated in the SHR. And when treated with i.c.v. ELE (12.5-25 ng/rat) they were far less sensitive than WKR to its antidipsogenic action on angiotensin-induced drinking. Smaller differences in strain sensitivity were also observed for the effect of ELE on cell dehydration- and on water deprivation-induced drinking, but only at the dose of 200 and 50 ng/rat, respectively. The different sensitivity of the SHR to the antidipsogenic effect of ELE supports the idea that tachykininergic mechanisms for control of water intake are differently regulated in the SHR than they are in the normotensive WKR.
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PMID:Sensitivity of spontaneously hypertensive and of Wistar Kyoto rats to the antidipsogenic action of eledoisin. 232 4

In infant rats, kassinin exerts its antidipsogenic effect in the very early stages of neonatal life (2nd-3rd day). The inhibition of cell-dehydration drinking appears in rats of 2 days, and attains adult levels in pups of 9 days. Instead, the thirsts induced by suckling deprivation or by intracerebroventricular angiotensin II are inhibited by kassinin precociously (3rd day), but are unaffected by it in rats of 12-15 days. Kassinin also inhibits milk intake very early (3rd day) and this effect also disappears at 12 days of age. The pattern of ontogenetic results described here may be that of a brain kassinin-like tachykinin that, in the course of the development of the neural structures on which it acts, gains potent and selective control of cell-dehydration thirst.
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PMID:The development in infant rats of kassinin's potent and selective control of cell-dehydration thirst. 274 16

The effects of various biologically active peptides on net jejunal water and electrolyte fluxes were studied in dogs in vivo. Vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), glucagon, gastrin, bombesin and neurotensin all had secretagogue activity, while methionine enkephalin stimulated net absorption. Somatostatin had no effect on net basal water and electrolyte transport, but inhibited glucagon-stimulated secretion. Secretin, calcitonin, substance P and pancreatic polypeptide (PP) did not have any effect on net water and electrolyte transport in the doses used in these experiments. The precise role played by these peptides in the control of intestinal transport has still to be determined. Studies in man have confirmed that food in the proximal small bowel stimulates secretion at sites remote from the application of food, and abnormal secretion of some peptides (e.g. VIP) has been associated with diarrhoea. Somatostatin has been used successfully to reduce the volume of certain types of secretory diarrhoea. Methods used in these experiments have been applied to the study of the composition and absorption characteristics of solutions used for oral rehydration in diarrhoea and in exercise-induced dehydration. Glucose polymers have been shown to be absorbed as rapidly as glucose from the jejunum.
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PMID:The effect of luminal and hormonal factors on small intestinal water and electrolyte transport. 287 15

Specific acetylcholinesterase and non-specific cholinesterases are present in all three lobes of the rat pituitary gland. This paper describes two new observations on hypophyseal acetylcholinesterase. Firstly, a prolonged increase of neurohormone secretion evoked by dehydration and sodium loading was accompanied by a decrease in the acetylcholinesterase activity localized to the neural lobe, where acetylcholinesterase has previously been demonstrated in fine nerve fibres. Secondly, electrical stimulation of the pituitary stalk in vitro elicited the release of acetylcholinesterase and non-specific cholinesterases from the combined neural and intermediate lobe indicating that the enzyme can be released from nerve endings in the hypophysis by action potentials. The observed loss of enzyme activity during dehydration may be the consequence of a prolonged activation of cholinergic nerves in the gland, leading to an increased release of acetylcholinesterase, which is not immediately replaced by fresh enzyme. The decrease in acetylcholinesterase in the neural lobe during dehydration may also be connected with its peptidase function and thus with the previously observed loss of substance P from the neural lobe during dehydration [Holzbauer et al. (1984) Neurosci. Lett. 47, 23-28].
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PMID:Acetylcholinesterase in the rat neurohypophysis is decreased after dehydration and released by stimulation of the pituitary stalk. 361 40

In the tubero-hypophyseal system of the rat the approximate concentrations of immunoreactive substance P (I-SP), expressed as fmol/mg tissue, were 100 in the medial basal hypothalamus (MBH), 20 in the anterior lobe (AL), 20 in the neural lobe (NL) and 4 in the intermediate lobe of the hypophysis. These values were not altered by treatment with capsaicin on day 2 after birth. In rats in which the secretion of neurohormones from the NL was increased by dehydration followed by sodium loading there was a fall by 70% in the I-SP concentration of the NL; no change occurred in the AL or the MBH.
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PMID:Immunoreactive substance P in the tubero-hypophyseal system of the rat: selective decrease in the neural lobe after dehydration and sodium loading. 620 29

Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptides in cardiovascular control. 640 Mar 63

Neuropeptide gamma (NP gamma) is a 21 aminoacid peptide belonging to the tachykinin (TK) family and including neurokinin A (NKA) in its C-terminal sequence. NP gamma possesses higher affinity than NKA for central NK-2 receptors; it shows lower affinity for NK-1 receptors, however, it potently stimulates salivary secretion, which is mediated by NK-1 receptor activation. Pulse intracerebroventricular (pICV) injection of TKs selectively inhibits water intake in rats. Our studies have suggested that NK-1 receptors may mediate the inhibition of angiotensin II-induced drinking, while NK-2 receptors that of drinking induced by cell dehydration. The present study evaluated the effect of pICV injections of NP gamma on water intake in rats. The injection of NP gamma, 8-250 ng/rat, markedly inhibited angiotensin II-induced drinking, and its effect was blocked by the NK-1 receptor antagonist WIN 62577. NP gamma potently inhibited also drinking induced by SC hypertonic NaCl load or water deprivation. The threshold dose for these effects was 31 ng/rat. Also carbachol-induced drinking was inhibited, but at higher doses. On the other hand, NP gamma did not modify food intake in food deprived rats or 0.1% saccharin intake in water and food sated rats, at the same doses effective on drinking. Present findings support the idea that TKs selectively inhibit water intake in rats and are in keeping with our hypothesis that NK-1 and NK-2 receptors mediate, respectively, inhibition of angiotensin II- and cell dehydration-induced drinking.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide gamma: a mammalian tachykinin endowed with potent antidipsogenic action in rats. 858 70

A method for the analysis of the substance P antagonist ezlopitant and two active metabolites in serum using solid-phase extraction followed by GC-MS analysis is described. The linear dynamic range was 1.0 to 100 ng/ml and precision and accuracy over this range were within 15%. Upon injection of reconstituted sample extracts into the hot injector port of the gas chromatograph, the benzyl alcohol metabolite undergoes a small amount of spontaneous dehydration to the alkene metabolite. We have incorporated an additional hexadeuterated internal standard of the benzyl alcohol into the assay to permit measurement of the extent of dehydration in each sample. This novel approach should be generally applicable to the simultaneous determination of benzyl alcohols and corresponding alkenes by GC-MS when the possibility exists that the alcohol can undergo spontaneous dehydration to the alkene in the injector port of GC instrumentation.
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PMID:Assay of ezlopitant, a substance P receptor antagonist, and metabolites in biological matrices by gas chromatography with mass spectrometric detection: simultaneous analysis of a benzyl alcohol and alkene. 1099 22

Intestinal secretion is a normal phenomenon, indispensible to solubilize and dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins and certain drugs may disrupt the proabsorptive status maintained by the small intestine under physiologic conditions. Hormones found in nervous and specialized intestinal enterochromaffin cells are responsible, in part, for secretion of fluid into the lumen. Afferent vagal nerve impulses mediated by 5-hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and substance P are the major agents of secretory stimulation. Toxins from pathogenic bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory response and a chain of events involving cGMP and cAMP which result in chloride secretion, coupled to sodium and fluid efflux into the lumen. If secretion is unchecked by natural mechanisms or medications, the consequences are diarrhea, with potential dehydration, hyponatremia and ultimately death. Introduction of absorbable nutrients in the intestinal lumen has a major antisecretory action, both by a nutrient-gene interaction and by proabsorptive hormone expression. In additon, during the absorptive process water is carried into the enterocyte together with solutes. Hydrolysis-resistant peptides of dietary origin and ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal system has a variety of antisecretory or proabsorptive hormonal and protein agonists that balance the outflow of fluid and electrolytes. The more extensively studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in secretion by activating cGMP. The intracellular concentration of NO may regulate the absorptive/secretory status of the small intestine, either stimulating absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist drugs and other pharmacologic agents have been clinically tried for the treatment of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.
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PMID:Regulation mechanisms of intestinal secretion: implications in nutrient absorption. 1198 1


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