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)

Exocrine cells secrete granule proteins by regulated or constitutive-like secretory pathways. It is thought that all secretory proteins can enter immature secretory granules in exocrine cells. To test this hypothesis, we expressed the constitutive secretory protein secreted alkaline phosphatase (SEAP) in the exocrine cell line AR42J and compared its secretion to that of amylase, an endogenous regulated secretory protein. Secretion of SEAP and amylase were stimulated about 1.5-fold by substance P and 2-fold by barium chloride. In dexamethasone-treated cells, SEAP and amylase secretion were stimulated about 1.8-fold by substance P, 5-fold by barium chloride, and 4-fold by cholecystokinin-8. Cycloheximide reduced basal secretion of SEAP and amylase by 50%, increasing cholecystokinin-stimulated secretion to about 10-fold. Sodium butyrate induced expression of SEAP 2-fold but had no effect on stimulated secretion. These results suggest that SEAP is stored in secretory granules in AR42J cells.
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PMID:Sorting of a constitutive secretory protein to the regulated secretory pathway of exocrine cells. 1019 48

Rab3 proteins (isoforms A, B, C and D) are low molecular weight GTP-binding proteins proposed to be involved in regulated exocytosis. In the present study, Rab3 protein expression and localization was examined in rat parotid gland by reverse transcription (rt) PCR, Western blotting and immunocytochemistry. An approximately 200 bp PCR product was obtained from parotid RNA by rtPCR and this fragment was cloned and sequenced. Nucleotide and deduced amino acid sequences obtained from five clones were identical to rab3D. Membrane and cytosolic fractions prepared from parotid acini were immunoblotted with antisera specific for each of the four Rab3 isoforms. A 28 kDa protein was detected with Rab3D-specific antisera in both fractions with staining being more intense in the membrane fraction. No other Rab3 isoforms were detected by immunoblotting, a result consistent with those obtained by rtPCR. Rab3D was enriched in zymogen granule membranes and Triton X-114 extraction revealed that this isoform is predominantly lipid-modified in parotid. Localization of Rab3D was done on frozen sections of parotid gland by immunofluorescence microscopy. Staining was observed primarily in the acinar cells and was adjacent to the acinar lumen. Incubation of dispersed acini with isoproterenol and substance P stimulated amylase secretion 4- and 2-fold above basal, respectively. Isoproterenol, but not substance P, induced redistribution of Rab3D from the cytosol to the membrane fraction in dispersed parotid acini. Consistent with these findings, isoproterenol injections into fasted rats also resulted in increased membrane-associated Rab3D in the parotid acini. These results indicate that Rab3D is: (1) the major Rab3 isoform expressed in rat parotid gland; (2) localized to zymogen granule membranes; and (3) involved with regulated enzyme secretion in acinar cells.
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PMID:Expression and localization of Rab3D in rat parotid gland. 1039 46

Although it is well known that somatostatin (SRIF) modulates several digestive functions, there are only a few reports about its effect on the salivary glands. Here, the action of SRIF parotid secretion was studied, in vivo and in vitro, in male Wistar rats. In vivo SRIF infusion (35 microg/kg per hr) inhibited the parotid flow rate stimulated by methacholine, substance P and noradrenaline. The isoprenaline-stimulated flow rate was also decreased by SRIF, but only at highest dose of the secretory agent. Total protein and amylase secretion were studied. SRIF inhibited the total protein secretion stimulated by the above-mentioned agents, except that by isoprenaline. SRIF did not inhibit in vivo amylase secretion. In order to avoid flow-rate interference with total protein and amylase measurements, in vitro experiments were performed. SRIF (25 nM) strongly inhibited the total protein release stimulated by methacholine (5.1 microM), noradrenaline (19 microM), and substance P (10 microM). The inhibitory effect was not raised by the absence of calcium in the incubation medium. However, in vitro amylase release was not affected by SRIF. It was concluded that SRIF modulates rat parotid secretion stimulated by cholinergic, adrenergic and peptidergic agents, acting on any step in the calcium pathway.
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PMID:Modulation by somatostatin of rat parotid salivary secretion stimulated by cholinergic, adrenergic and peptidergic agents. 1041 70

Vertebrate gastrointestinal hormones were tested on their ability to liberate digestive enzymes from the crustacean midgut gland. CCK-8 (desulfated form), gastrin, bombesin, secretin, and substance P were detected to release enzymes. Maximal concentrations observed were 5 nM CCK for protease release, 1 nM gastrin for protease and 100 nM for amylase release, 100 nM bombesin for protease release, 10 nM secretin for amylase and protease release, and 100 nM substance P for protease release. Unlike in vertebrates, glucagon was unable to stimulate enzyme release in crustaceans, this also applies to the counterpart insulin. These results may support the assumption that Crustacea possess endogenous factors resembling the above mentioned vertebrate hormones, at least in such a way that the appropriate receptors have the capacity to accept these hormones.
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PMID:Release of digestive enzymes from the crustacean hepatopancreas: effect of vertebrate gastrointestinal hormones. 1042 22

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10(-10) M SP to the perfusate, and maximal inhibition was seen with 10(-8) M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.
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PMID:Substance P inhibits pancreatic exocrine secretion via a neural mechanism. 1044 45

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1-R agonists/antagonists in rats and NK1-R(+/+)/(-/-) mice. The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized. In rats, both SP and the NK1-R selective agonist [Sar(9) Met(O(2))(11)]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1-R antagonist CP 96,345. Selective agonists of the NK-2 or NK-3 receptors had no effect. In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1-R antagonist CP 96,345. In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1-R knockout mice. In NK1-R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals. Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis.
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PMID:Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. 1082 77

Amylase secretion from parotid acinar cells results from stimulus-regulated fusion of apical membrane and secretory granules that contain amylase. The time course of amylase secretion induced by various secretagogues has been reported. Calcium-mobilizing agonists such as carbamylcholine and substance P induce rapid and transient secretion while cAMP-mobilizing agonists such as isoproterenol cause long-term secretion. Combination of these two types of agonists results in a rapid and high rate of secretion. To explain the various time courses of these stimulations, it was assumed that amylase secretion is a consecutive reaction that consists of two first-order reactions. It was postulated that secretory granules were classified into three states: (A) pre-docked, (B) docked, and (C) fusion. The simple simulation could explain the time course of amylase secretion induced by various secretagogues by simply changing the rate constants for docking (reaction A to B) and fusion (reaction B to C) steps. It was also found that calcium mainly enhances the last fusion step and that cAMP activates the docking step. The amount of docked granules is estimated to be quite small, which accounts for why amylase secretion is regulated mainly by cAMP. The effects of the two types of secretagogues were synergistic, meaning that their intracellular signaling pathways are independent. At the same time, this also suggests that basal and enhanced secretion induced by two types of agonists have the same exocytotic process and that two stimuli independently activate the same machinery that mediates docking or fusion. This simulation is useful in analysis of the effects of secretion modulators and the molecular mechanism of amylase secretion.
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PMID:Simulation of regulated exocytosis of amylase from salivary parotid acinar cells by a consecutive reaction model comprising two sequential first-order reactions. 1088 99

We examined whether the capsaicin vanilloid receptor-1 (VR1) mediates substance P (SP) release from primary sensory neurons in experimental pancreatitis. Pancreatitis was achieved by 12 hourly injections of caerulein (50 microg/kg ip) in mice. One group received capsazepine (100 micromol/kg sc), a competitive VR1 antagonist, at 4-h intervals. Neurokinin-1 receptor (NK1R) internalization in acinar cells, used as an index of endogenous SP release, was assessed by immunocytochemical quantification of NK1R endocytosis. The severity of pancreatitis was assessed by measurements of serum amylase, pancreatic myeloperoxidase (MPO) activity, and histological grading. Caerulein administration caused significant elevations in serum amylase and pancreatic MPO activity, produced histological evidence of pancreatitis, and caused a dramatic increase in NK1R endocytosis. Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis. These results demonstrate that repeated caerulein stimulation causes experimental pancreatitis that is mediated in part by stimulation of VR1 on primary sensory neurons, resulting in endogenous SP release.
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PMID:Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. 1166 42

Vasoactive intestinal peptide (VIP, 4 microg kg(-1) min(-1)), substance P (3 microg kg(-1) min(-1)) and neurokinin A (2.5 microg kg(-1) min(-1)) were infused intravenously for 30 min in anaesthetized rats and the effects of these peptides on the parotid gland were examined. VIP reduced the numerical density of parotid acinar secretory granules, storing proteins, by 29 % and the glandular amylase activity by 33 %. Substance P reduced the number of secretory granules by 18 % but the amylase activity was unchanged. These results make VIP and substance P likely contributors to the parasympathetic non-adrenergic, non-cholinergic (NANC)-evoked parotid acinar degranulation. Neurokinin A, on the other hand, caused no reduction in granular number but reduced the glandular amylase activity by 19 %, indicating vesicular protein secretion.
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PMID:Acinar degranulation in the rat parotid gland induced by neuropeptides. 1169 67

The tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-tachykinin receptor agonist, and senktide, a synthetic NK3-tachykinin receptor agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6)M), PG-KII and senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5+/-0.8 and 8.1+/-0.6% of the total lobular amylase content) than carbachol (34.4+/-3.9%), caerulein (26.5+/-2.8%) and KCl (22.5+/-3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK3 receptor antagonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10(-7)M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10)M) and carbachol (10(-7) and 10(-6)M). These findings show that PG-KII and senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 receptors, without cholinergic involvement. We suggest also that the tachykininergic NK3 receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.
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PMID:Selective tachykinin NK3-receptor agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig. 1208 27


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