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)

12-O-tetradecanoylphorbol-13-acetate (TPA, 1 to 30 ng/ml) produced a dose-related inhibition of substance P (SP)-induced histamine release from rat peritoneal mast cells. TPA itself induced some histamine release over this concentration range (maximum release about 20% of total). Maximum inhibition of SP-induced release by TPA required preincubation with TPA for at least 10 min. The inhibitory action of TPA was observed in the absence as well as in the presence of extracellular calcium (0.4 mM). Inhibition of diacylglycerol kinase by R 59022 or of diacylglycerol lipase by RHC 80267 reduced SP-induced histamine release. Oleolylacetylglycerol (OAG, 50 microM) inhibited histamine release induced by SP but was less potent than TPA. It is concluded that protein kinase C activation in rat peritoneal mast cells is associated with inhibition of SP-induced histamine release.
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PMID:Effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on substance P-induced histamine release from rat peritoneal mast cells. 169 35

R 59022, a compound which causes the accumulation of diacylglycerol by inhibition of the enzyme diacylglycerol kinase, was tested for its effect on stimulated motor activity of the longitudinal muscle from the guinea-pig ileum. Motor responses to histamine were very potently inhibited by R 59022 (greater than or equal to 0.03 microM), which confirms its known activity as a histamine receptor antagonist. Contractions elicited by acetylcholine, substance P, or K+ depolarization were also concentration dependently depressed by R 59022 (1-30 microM); further analysis showed that substance P was antagonized in a non-competitive manner. R 59022 was significantly more active to block the tonic than the phasic component of the contractile response to K+ depolarization. The Ca2+-induced activation of the contractile apparatus in chemically skinned muscle strips was depressed by similar concentrations of R 59022 (3-30 microM). These data indicate that R 59022 suppresses the contractile activity of intestinal smooth muscle at an intracellular site of action but it is not yet clear whether this action can be accounted for by the accumulation of diacylglycerol and subsequent stimulation of protein kinase C.
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PMID:The diacylglycerol kinase inhibitor, R 59022, suppresses contractility of intestinal smooth muscle. 246 9