Tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), have been shown to be epimerized to (-)-catechin (C), (-)-gallocatechin (GC), (-)-catechin gallate (CG), and (-)-gallocatechin gallate (GCG), respectively, during heat treatment. In this study, we examined the effect of tea catechins rich in ECG and EGCG and heat-treated tea catechins rich in CG and GCG on postprandial hypertriacylglycerolemia in rats. Both tea catechins and heat-treated tea catechins suppressed postprandial hypertriacylglycerolemia. Lymphatic recovery of (14)C-trioleoylglycerol in rats cannulated in the thoracic duct was delayed by the administration of tea catechins and heat-treated tea catechins. Tea catechins and heat-treated tea catechins had the same effect on all variables tested. These catechin preparations dose-dependently inhibited the activity of pancreatic lipase in vitro. When purified catechins were used, only those with a galloyl moiety inhibited the activity of pancreatic lipase. These results suggest that catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by slowing down triacylglycerol absorption through the inhibition of pancreatic lipase. Because postprandial hypertriacylglycerolemia is a risk factor for coronary heart disease, our results suggest that catechins with a galloyl moiety may prevent this disease.

1 Isometric contractile responses to carbachol were studied in ileal longitudinal smooth muscle strips from wild-type mice and mice genetically lacking M 2 or M 3 muscarinic receptors, in order to characterize the mechanisms involved in M 2 and M 3 receptor-mediated contractile responses. 2 Single applications of carbachol (0.1-100 mM) produced concentration-dependent contractions in preparations from M 2 -knockout (KO) and M 3 -KO mice, mediated via M 3 and M 2 receptors, respectively, as judged by the sensitivity of contractile responses to blockade by the M 2 -preferring antagonist methoctramine (300 nM) or the M 3 -preferring antagonist 4-DAMP (30 nM). 3 The M 2 -mediated contractions were mimicked in shape by submaximal stimulation with high K þ concentrations (up to 35 mM), almost abolished by voltage-dependent Ca 2 þ channel (VDCC) antagonists or depolarization with 140 mM K þ medium, and greatly reduced by pertussis toxin (PTX) treatment. 4 The M 3 -mediated contractions were only partially inhibited by VDCC antagonists or 140 mM K þ -depolarization medium, and remained unaffected by PTX treatment. The contractions observed during high K þ depolarization consisted of different components, either sensitive or insensitive to extracellular Ca 2 þ . 5 The carbachol contractions observed with wild-type preparations consisted of PTX-sensitive and -insensitive components. The PTX-sensitive component was functionally significant only at low carbachol concentrations. 6 The results suggest that the M 2 receptor, through PTX-sensitive mechanisms, induces ileal contractions that depend on voltage-dependent Ca 2 þ entry, especially associated with action potential discharge, and that the M 3 receptor, through PTX-insensitive mechanisms, induces contractions that depend on voltage-dependent and -independent Ca 2 þ entry and intracellular Ca 2 þ release. In intact tissues coexpressing M 2 and M 3 receptors, M 2 receptor activity appears functionally relevant only when fractional receptor occupation is relatively small.

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1 The effects on the whole-cell carbachol-induced muscarinic cationic current (mIcat) of antibodies against the a-subunits of various G proteins, as well as the effect of a Gbg subunit, were studied in single guinea-pig ileal smooth muscle cells voltage-clamped at À50 mV. Ionized intracellular calcium concentration, [Ca 2+ ] i , was clamped at 100 nM using a 1,2-bis(2-aminophenoxyl-ethane-N,N,N 0 ,N 0 -tetraacetic acid)/Ca 2+ mixture. 2 Application of ascending concentrations of carbachol (1 -300 mM) activated mIcat (mean amplitude 0.83 nA at 300 mM carbachol; EC 50 8 mM; Hill slope 1.0). A 20 min or longer intracellular application via the pipette solution of G i3 /G o or G o antibodies resulted in about a 70% depression of the maximum response without change in the EC 50 value. In contrast, antibodies against a-subunits of G i1 , G i1 /G i2 , G i3 , G q /G 11 or G s protein over a similar or longer period did not significantly reduce mIcat. Antibodies to common Gb or infusion of the Gbg subunit itself had no effect on mIcat.3 If cells were exposed briefly to carbachol (50 or 100 mM) at early times (o3 min) after infusion of antibodies to Ga i3 /Ga o or to Ga o had begun, carbachol responses remained unchanged even after 20 -60 min; that is, the depression of mIcat by these antibodies was prevented. 4 These data show that Ga o protein couples the muscarinic receptor to the cationic channel in guinea-pig ileal longitudinal smooth muscle and that Gbg is not involved. They also show that prior activation of the muscarinic receptor presumably causes a long-lasting postactivation change of the G protein, which is not reflected in mIcat, but acts to hinder antibody binding.

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