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)

Adrenergic and osmoregulatory responses to substance P (SP) were studied in salt-loaded ducks. SP inhibited nasal salt secretion by decreasing the salt concentration of the nasal fluid, but reversed the inhibitory effect of angiotensin II (ANG II) on nasal water and K secretion. SP also stimulated salivation, urinary water excretion, and urinary salt excretion, but diminished the diuretic and saluretic responses to ANG II. The osmoregulatory effects of SP were accompanied by elevated plasma concentrations of norepinephrine and epinephrine. The data suggest that SP may contribute to adrenergic and osmotic regulation in ducks.
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PMID:Reevaluation of the effect of substance P on nasal salt gland secretion in the duck (Anas platyrhynchos). 244 66

The tachykinin peptide [Asp5.6, MePhe8]substance P(5-11) (NH2-senktide), a senktide analogue lacking the N-terminal succinyl group, is a selective and metabolically stable NK-3 receptor agonist. In the present study it potently inhibited salt appetite induced by sodium depletion in rats. Argo-neurokinin B, too, inhibited salt appetite, but was less potent than NH2-senktide. Neither peptide inhibited drinking behaviour induced by subcutaneous hypertonic NaCl. NH2-senktide slightly inhibited angiotensin-induced drinking, while Argo-neurokinin B was ineffective. On the other hand, eledoisin was a potent inhibitor in the 3 behavioural tests. Present results indicate that activation of NK-3 receptors is involved in the antinatriorexic action of tachykinins, and that different receptor subtypes might be involved in the different effects of tachykinins on the rat ingestive behaviour.
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PMID:The tachykinin NH2-senktide, a selective neurokinin B receptor agonist, is a very potent inhibitor of salt appetite in the rat. 246 99

The goal of this study was to examine myogenic responses of isolated porcine subepicardial and subendocardial arterioles (80-100 micron in diameter) within physiological ranges of intraluminal pressure. Arterioles were located by perfusion with india ink-gelatin solution then dissected and cannulated with glass micropipettes. Intraluminal pressure was altered in 20-cmH2O steps over the range of 20-140 cmH2O. IN physiological salt solution (36-37 degrees C), the coronary arterioles developed spontaneous tone and exhibited myogenic responses. At the lower pressures (20-60 cmH2O), subendocardial arterioles responded passively (diameter decreased from a control diameter at 60 cmH2O), whereas subepicardial arterioles maintained their diameters. At higher pressures (100-140 cmH2O), both subepicardial and subendocardial arterioles demonstrated myogenic constriction, but subepicardial arterioles demonstrated greater myogenic constriction than subendocardial arterioles. This implies that myogenic autoregulation in subepicardial arterioles is better than that in the subendocardial arterioles at both low and high pressures. In the presence of nitroprusside (10(-4) M), all arterioles responded to pressure changes passively, and there were no differences between subepicardial and subendocardial vessels. The functional integrity of the endothelium was verified by relaxation to substance P (10(-7) M). This is the first in vitro study to demonstrate coronary myogenic activity and transmural differences in these arteriolar responses. Our data support the concept that myogenic mechanisms in 80 to 100-micron arterioles may actively contribute to autoregulation of coronary blood flow.
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PMID:Myogenic activity in isolated subepicardial and subendocardial coronary arterioles. 246 67

The dual effect of capsaicin on primary afferent neurons, excitation and stimulation of transmitter release, its dependence on extracellular calcium and its modulation by Ruthenium Red have been investigated in the rabbit ear. Injection of capsaicin into the central artery of the isolated perfused ear with intact neuronal connection induced a reflex fall in systemic arterial blood pressure of the anaesthetized rabbit. Addition of Ruthenium Red (0.6-20 microM) to the perfusate of the ear reversibly attenuated this response in a dose-dependent manner. Perfusion of the ear with a Ca2+-free, 3 mM EGTA-containing physiological salt solution enhanced the capsaicin-evoked depressor reflex but did not prevent the inhibitory action of Ruthenium Red. Perfusion of the isolated rabbit ear with capsaicin (10 microM)-containing physiological salt solution induced the release of substance P-like immunoreactivity which was inhibited by Ruthenium Red (0.6-20 microM) and by omission of extracellular Ca2+. The results demonstrate that capsaicin-evoked transmitter release is dependent on extracellular calcium while capsaicin-evoked excitation is not reduced in a Ca2+-free perfusate. Both effects of capsaicin are potently inhibited by Ruthenium Red. The fact that capsaicin-induced excitation of primary afferents is antagonized by Ruthenium Red also in the absence of extracellular Ca2+ suggests this inhibitory action of Ruthenium Red is not only mediated by inhibition of transmembrane Ca2+ fluxes.
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PMID:Capsaicin-induced stimulation of polymodal nociceptors is antagonized by ruthenium red independently of extracellular calcium. 247 80

The present study investigates the effect of the mammalian tachykinin neurokinin A on salt intake in the rat. Intracerebroventricular injection of neurokinin A inhibited salt intake elicited by sodium depletion, by subchronic deoxycorticosterone treatment and by adrenalectomy. It also inhibited the need-free salt intake of female rats that had been previously depleted of sodium. Since different brain mechanisms elicit salt intake in these experimental models, it is concluded that neurokinin A exerts a general antinatriorexic effect. Apparently, its inhibitory effect on salt intake is not due to malaise or competing behaviors, as shown by the fact that the doses of neurokinin A which suppress salt intake do not suppress milk intake. In comparison to the amphibian tachykinin kassinin, neurokinin A possesses a similar spectrum of antinatriorexic activities, but is markedly less potent and less effective in all the experimental models investigated. These findings suggest that activation of neurokinin A receptors cannot solely account for the potent antinatriorexic effect of kassinin and of other nonmammalian tachykinins.
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PMID:Suppression of salt intake in the rat by neurokinin A: comparison with the effect of kassinin. 254 May 11

From the soluble and membrane fractions of rat brain homogenate, two enzymes that liberate dipeptides of the type Xaa-Pro from chromogenic substrates were purified to homogeneity. The two isolated dipeptidyl peptidases had similar molecular and catalytic properties: For the native proteins, molecular weights of 110,000 were estimated; for the denatured proteins, the estimate was 52,500. Whereas the soluble peptidase yielded one band of pI 4.2 after analytical isoelectric focusing, two additional enzymatic active bands were detected between pI 4.2 and 4.3 for the membrane-associated form. As judged from identical patterns after neuraminidase treatment, both peptidases contained no sialic acid. A pH optimum of 5.5 was estimated for the hydrolysis of Gly-Pro- and Arg-Pro-nitroanilide. Substrates with alanine instead of proline in the penultimate position were hydrolyzed at comparable rates. Acidic amino acids in the ultimate N-terminal position of the substrates reduced the activities of the peptidases 100-fold as compared with corresponding substrates with unblocked neutral or, especially, basic termini. The action of the dipeptidyl peptidase on several peptides with N-terminal Xaa-Pro sequences was investigated. Tripeptides were rapidly hydrolyzed, but the activities considerably decreased with increasing chain length of the peptides. Although the tetrapeptide substance P 1-4 was still a good substrate, the activities detected for the sequential liberation of Xaa-Pro dipeptides from substance P itself or casomorphin were considerably lower. Longer peptides were not cleaved. The peptidases hydrolyzed Pro-Pro bonds, e.g., in bradykinin 1-3 or 1-5 fragments, but bradykinin itself was resistant. The enzymes were inhibited by serine protease inhibitors, like diisopropyl fluorophosphate or phenylmethylsulfonyl fluoride, and by high salt concentrations but not by the aminopeptidase inhibitors bacitracin and bestatin. Based on the molecular and catalytic properties, both enzymes can be classified as species of dipeptidyl peptidase II (EC 3.4.14.2) rather than IV (EC 3.4.14.5). However, some catalytic properties differentiate the brain enzyme from forms of dipeptidyl peptidase II of other sources.
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PMID:Purification of two dipeptidyl aminopeptidases II from rat brain and their action on proline-containing neuropeptides. 256 25

The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth muscle functions, it is not known whether similar stimuli also influence salt and water transport as a meal traverses the alimentary canal.
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PMID:Intestinal nerves and ion transport: stimuli, reflexes, and responses. 257 77

The neuromodulatory action of adenosine and ATP was investigated in isolated guinea pig bronchial strip chain preparations contracted with electrical field stimulation. The tissues were placed in organ baths containing physiological salt solution and stimulated at 8-Hz frequency, 0.5-ms pulse duration, and 30 V (approximately 100 mA) for 5 s. Electrical field stimulation evoked a biphasic contraction of bronchial muscle, consisting of an initial contraction followed by a sustained contraction, which was mediated by intramural cholinergic and noncholinergic nerve stimulations, respectively. Adenosine, at concentrations greater than M, caused a concentration-dependent inhibition in the height of the noncholinergically mediated contraction, accompanied by a very weak inhibition on the cholinergically mediated response. ATP (10(-5) to 3 x 10(-3) M) also produced a similar inhibitory effect on the noncholinergically mediated contraction, but the inhibitory potency was less than that of adenosine. The inhibitory response to adenosine was enhanced by the pretreatment with dipyridamole (2 x 10(-6) M) but antagonized with aminophylline (10(-5) M). Contractions of bronchial muscle evoked by exogenous acetylcholine (2 x 10(-6) M) or substance P (2 x 10(-7) M) were significantly inhibited by the adenosine (3 x 10(-4) M) pretreatment. These data suggest that in isolated guinea pig bronchi adenosine selectively inhibits noncholinergic neurotransmission through prejunctional P1-purinoceptors.
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PMID:Adenosine selectively inhibits noncholinergic transmission in guinea pig bronchi. 274 77

Sialoadenectomized and sham-operated rats were given salivary secretory stimulants 30 min prior to intragastric instillation of a bile salt solution (5 mM-sodium taurocholate in 100 mM-HCl). Administration of the alpha-agonist phenylephrine (0.15-15 mg/kg) resulted in a dose-dependent reduction in the loss of H+ and the intraluminal appearance of Na+ and K+ associated with bile-salt-induced damage to the stomach in the sham-sialoadenectomized rat. The effect was not apparent if the salivary glands had been previously excised. Adrenaline (0.8-4.0 mg/kg) and noradrenaline (0.8-4.0 mg/kg) were less effective in reducing the degree of mucosal damage in sham-sialoadenectomized rats and were not effective in sialoadenectomized rats. Administration of secretory stimulant doses of isoprenaline (5 mg/kg), pilocarpine (2 mg/kg) and substance P (25 mg/kg) either had no significant effect or exacerbated the net transmucosal fluxes of H+, Na+ and K+ associated with bile salt damage to the gastric mucosa. The protective action of phenylephrine in sham-sialoadenectomized rats was reversed by prior treatment with the alpha-antagonist, phentolamine (2 mg/kg). The effect of phentolamine was dose dependent. Vagotomy abolished the protective influence of phenylephrine in sham-sialoadenectomized rats but did not influence the response to other salivary secretory stimulants consistently. These data suggest that stimulation of alpha-adrenergic receptors in rat salivary tissue is associated with an amelioration of the increase in gastric mucosal permeability to H+, Na+ and K+ in response to an intraluminal bile salt solution. The apparent protective influence of alpha-adrenergic receptor activation in sham-sialoadenectomized rats is mediated in part by the vagus nerve.
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PMID:The effect of adrenergic, cholinergic and peptidergic salivary stimulants on gastric mucosal integrity in the rat. 288 55

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.
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PMID:Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms. 298 72


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