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)

The neuropeptide substance P (SP) produces transient elevations in short-circuit current (Isc), a measure of active ion transport, across sheets of small intestinal mucosae from several animal species, but the ionic basis of this action remains unknown. The aim of this study was to test the hypothesis that SP promotes electrogenic anion secretion in the porcine proximal jejunum, an intestinal segment analogous to the human upper small intestine. Sheets of jejunal mucosa with attached submucosa responded to serosal (S), but not luminal (L) addition of 0.1 microM SP with a transient increase in Isc that was reduced in tissues pretreated with the Na(+)-K(+)-Cl- cotransport inhibitor bumetanide (10 microM) or bathed in media lacking Cl- or HCO3- ions. SP produced biphasic effects on transepithelial Na+ and Cl- fluxes; it initially stimulated a L-directed Na+ secretory flux during a 5-min period in which peptide-induced Isc elevations were maximum. The return of the Isc to base-line levels was temporally associated with an increase in L-directed Cl- transport. Both effects of SP were absent in tissues either pretreated with the neuronal conduction blocker tetrodotoxin (0.1 microM) or bathed in HCO3(-)-deficient media. Bumetanide abolished the Na+ secretory actions of SP, but did not affect peptide-induced Cl- secretion. pH-Stat titration experiments revealed that mucosal sheets alkalinized the L bathing medium at a rate twice that of the S medium. SP simultaneously increased and suppressed L and S alkalinization, respectively; this effect presumably represents HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P produces sodium and bicarbonate secretion in porcine jejunal mucosa through an action on enteric neurons. 137 57

The effects of the non-mammalian tachykinin physalaemin were studied on the short circuit current (SCC) and on both influx (Ji) and outflux (Jo) of 36Cl- and 22Na+ across the isolated skin of Rana esculenta. Physalaemin, added to the internal bathing fluid, increased SCC in a dose-dependent manner with a maximal effect at 1 microM. This increase was due to a stimulation of both Na+ absorption and Cl- secretion. Bumetanide (20 microM in the internal fluid), an inhibitor of the Na+/K+/2Cl- cotransporter, reduced the action of physalaemin on SCC by 46%. Furthermore diphenylamine-2-carboxylic acid (DPC, 0.1 mM in the external fluid), an inhibitor of Cl- channels, decreased the effect of the peptide on SCC by 48%. It is concluded that physalaemin activates the Na+/K+/2Cl- cotransporter at the basolateral membrane, accumulating Cl- in the cells and favouring its exit through Cl- channels at the outermost membrane of the epithelium. An inhibitor of cyclooxygenases, i.e. naproxen, strongly inhibited the physalaemin effect on SCC, whereas 5,8,11-eicosatriynoic acid (ETI), an inhibitor of lipooxygenases was without effect. Therefore, it is proposed that prostaglandins (probably PGE2) are the cellular mediators of this action. An antagonist of NK1 receptors for tachykinins, CP 99,994, inhibited the physalaemin action on SCC, whereas challenge with SR 48,968, an antagonist of NK2 receptors, had no effect on physalaemin action. It is concluded that physalaemin effect on SCC in frog skin is mediated by its interaction with NK1 receptors.
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PMID:Action of physalaemin on the ionic transport across the frog skin. 971 52

The present study was undertaken to identify and determine the mechanism of noncholinergic pathways for the induction of liquid secretion across airway epithelium. Excised porcine bronchi secreted substantial and significant quantities of liquid when exposed to acetylcholine, substance P, or forskolin but not to isoproterenol, norepinephrine, or phenylephrine. Bumetanide, an inhibitor of Na(+)-K(+)-2Cl(-) cotransport, reduced the liquid secretion response to substance P by 69%. Approximately two-thirds of bumetanide-insensitive liquid secretion was blocked by dimethylamiloride (DMA), a Na(+)/H(+) exchange inhibitor. Substance P responses were preserved in airways after surface epithelium removal, suggesting that secreted liquid originated from submucosal glands. The anion channel blockers diphenylamine-2-carboxylate (DPC) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) inhibited >90% of substance P-induced liquid secretion, whereas DIDS had no effect. DMA, DPC, and NPPB had greater inhibitory effects on net HCO(3)(-) secretion than on liquid secretion. Although preserved relative to liquid secretion, net HCO(3)(-) secretion was reduced by 39% in the presence of bumetanide. We conclude that substance P induces liquid secretion from bronchial submucosal glands of pigs through active transport of Cl(-) and HCO(3)(-). The pattern of responses to secretion agonists and antagonists suggests that the cystic fibrosis transmembrane conductance regulator mediates this process.
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PMID:Mechanism of substance P-induced liquid secretion across bronchial epithelium. 1150 91