AIM Action of adenosine triphosphate(ATP)on longitudinal muscle strips of the rat distal colon has been reported, however, that of the rat proximal colon remains to be clarified. In this study we investigated the effects of ATP on longitudinal muscle strips isolated from the rat proximal colon and the receptors involved in the effects. METHODSIsometric relaxant and contractile responses to ATP (0.1 μmol · L- 1 - 1 mmol· L- 1 ) and adenosine (1 - 100 μmol· L-1) in longitudinal muscle strips of the rat proximal colon were observed. RESULTS ATP (0.1 μmol· L- 1 - 1 mmol· L- 1 ) produced a complicated response including an inhibition of rhythmic contraction and a weakly transient decrease in basic tone (0.05-0.08 g) followed by a concentration-dependent contraction (0.04- 0.44 g) in longitudinal muscle strips of the rat proximal colon at resting tension. Tetrodotoxin (0.1 μmol·L-1) did not influence the responses to ATP.Adenosine (1 - 100 μmol· L-1) did not produce an obvious contractile response in the preparation at resting tension. Concentration-dependent relaxant responses to ATP ( 1 μmol· L- 1 - 1 mmol· L- 1 ) in the preparation precon tracted with 5-hydroxytryptamine or with acetylcholine were 23.2％ - 94.6％ or 24.8 ％ - 92.4％, however the relaxant responses to adenosine were much weaker than those to ATP. CONCLUSION ATP produces contractileresponsesmainly via purine and pyrimidine (P) 2receptors and relaxant responses partially via P1 receptors in longitudinal muscle strips of the rat proximal colon.

Aim To investigate the effect of racemic-doxazosin(rac-DOX),S-doxazosin(S-DOX) and R-doxazosin(R-DOX) on the proliferation of vascular smooth muscle cells(VSMCs) of the rat aorta.Methods VSMCs of the rat aorta were cultured,MTT assay was used to determine the cell proliferation and the morphological changes in VSMCs were analyzed using Giemsa's staining.Results The treatment with rac-DOX,S-DOX or R-DOX at 3~30 ?mol?L-1 for 96 h inhibited the proliferation of VSMCs significantly.However,the inhibitory effect of S-DOX on cell proliferation was more potent than that of R-DOX at the same concentration(P

Extracellular adenosine triphosphate (ATP) and adenosine are important signaling molecules in both intracellular and extracellular microenviroments of cells. They exert cytoxic and apoptotic effects in some tissues such as tumor. The proapoptotic mechanisms of adenosine and its receptors are involved in Adenylyl cyclase(AC), cAMP, Ca 2+ , etc. Apoptosis induced by ATP is as sociated with several purinergic receptors including P2X_1, P2X_2, P2X_7, P2Y_1, P2Y_2, et al, it is also involved in FasL/FasR, T cell receptor(TCR), and gene regulations of bcl-2 and bax.

AIM To study the growth inhibition of adenosine triphosphate (ATP) and adenosine (ADO) on cultured tumor cells in vitro. METHODS MTT assays were used to determine the inhibition of proliferation of ATP and ADO on several tumor cell lines, including human squamous esophageal carcinoma cells TE-13, human stomach carcinoma cells HGC-27 and human erythroleukemia cells K562. The morphological changes of ATP and ADO on the cell lines were observed under light microscope. RESULTS ATP and ADO produced a certain inhibition effect on TE-13, HGC-27, K562 cells at different concentration between 0.01～1.0 mmol?L -1. The maxium inhibition fraction of TE-13, HGC-27, K562 cells exposed to ATP for 72 h was 80.52%, 58.67% and 45.07%, respectively; and to ADO for 72 h, was 74.03%, 52% and 30.99%, respectively. Under light microscope, the tumor cells exposed to higher concentration(1 mmol?L -1) of ATP and ADO displayed morphological changes of apoptosis. CONCLUSION These results suggested that ATP has a certain cytotoxic effect on several tumor cell lines, it might partly be related to ADO. Its mechanism might involve apoptosis.

AIM The effects of calcium antagonist diltiazem on plasma insulin levels were investigated in rats. METHODS Plasma insulin was measured with radioimmunoassay method. RESULTS In the fasting rat, plasma insulin levels were significantly increased after ig diltiazem 10 mg?kg -1 and 100 mg?kg -1 , and the level of plasma insulin was increased by 131% 30 min after administration of diltiazem 100 mg?kg -1 in comparison with that of control group. Diltiazem increased the plasma insulin level markedly in glucose tolerance test of the rat. In the hyperglycemia rat induced by adrenaline, diltiazem 100 mg?kg -1 weakly increased the plasma insulin level only at 1 h after administration. CONCLUSION Diltiazem increases the plasma insulin levels in the fasting rat and glucose loaded rat. The increase of plasma insulin level induced by diltiazem is due to the hyperglycemic action of diltiazem and other effect, probably a direct or an indirect insulin release action on pancreas of the rat.

Objective To discuss pathogenic effects of low high-density lipoprotein cholesterol(HDL-C)on atherosclerosis and thromboembolism,the influences of HDL-C on platelet cytosolic free calcium concentration([Ca2+]i),platelet release reaction products beta-thromboglobulin(?-TG)and platelet factor 4(PF4)were observed in dyslipoproteinemia patients with low HDL-C.Methods i,?-TG and PF4 were measured by fluorescent probe Fura 2-AM and ELISA skills respectively,in 42 patients with low HDLC(LHDL-C)and 25 healthy controls(CONT).Results Compared with those in CONT group,the platelet[Ca2+]i,?-TG and PF4 were all higher in LHDL-C group(all P

OBJECTlVE To investigate the effect of stretch on muscarinic receptor- and 5-hydroxytryptamine( 5-HT)receptor-mediated contractiIe responses in isoIated circuIar muscIe strips taken from the rat stomach. METHODS The contractiIe responses to carbachoI(CCh)0.001-30 μmoI·L-1 or 5-HT 0.0001 -30 μmoI·L-1 administered cumuIativeIy were recorded in isoIated circuIar muscIe strips taken from the gastric fundus,body,cardia and pyIorus of rats under different preIoads of 1.0,1.5,2.0, 2.5 and 3. 0 g,but a singIe concentration of CCh 0. 3 μmoI·L-1 was administered to the antrum. RESULTS The -Log EC50 vaIue for CCh in the isoIated circuIar muscIe strips of the gastric fundus, body and pyIorus under 1.0 g preIoad was the Iargest,but decreased significantIy with higher preIoads (P﹤0.05,P﹤0.01). A simiIar resuIt was obtained in the isoIated circuIar muscIe strips of the gastric body when 5-HT was used as an agonist. The Emax vaIue of contractiIe responses to CCh and 5-HT in the cir-cuIar muscIe strips of the gastric cardia under 3.0 g preIoad was increased by 117.4% and 75.7% com-pared to that under 1.0 g preIoad. The Emax vaIue of contractiIe responses to 5-HT in the circuIar muscIe strips of the gastric body under 3.0 g preIoad was aIso increased by 115.9% when compared to 1.0 g preIoad. The Emax( g) vaIue of contractiIe responses to CCh in four types of muscIe strips was 10.453±2.956(cardia under 3.0 g preIoad),13.878±2.618(fundus under 2.5 g preIoad),10.244±1.843 (gastric body under 2.5 g preIoad)and 2.585±1.098(pyIorus under 2.5 g preIoad),respectiveIy. The Emax(g)vaIue of contractiIe responses to 5-HT in three types of muscIe strips was 4.363±1.705(cardia under 3.0 g preIoad),3.931±0.615(fundus under 3.0 g preIoad)and 3.161±0.680(gastric body under 3.0 g preIoad),respectiveIy. CONCLUSlON 0.5 g or 1.0 g preIoad is inadequate for accurate determi-nation of contractiIe responses mediated by muscarinic receptors and 5-HT receptors in isoIated circuIar muscIe strips taken from the rat gastric cardia,fundus,body and pyIorus,but 2.0 g preIoad is optimaI for investigating muscarine receptor- or 5-HT receptor-mediated contractiIe responses of isoIated gastric strips of rats.

P-glycoprotein (P-gp) is an ATP-dependent multidrug efflux pump that acts as a major obstacle for oral drug delivery and cancer therapy. Recent reports have provided evidence that excipients often used in pharmaceutical formulations, such as Pluronic and TPGS, also have inhibitory effects on P-glycoprotein. Because inhibition of efflux transporters by polymeric inhibitors may dramatically increase the bioavailability of P-gp substrates with negligible side effects, identification of the mechanism and their structure activity relationship is therefore of significant importance for pharmaceutical development. Other than competitive inhibition for traditional inhibitors, polymeric inhibitors may modify P-gp function through alterations on membrane fluidity, inhibition of P-gp ATPase, depletion of intracellular ATP and down-regulating of P-gp expression. In the present review, the inhibition mechanism of potential polymeric inhibitors and their structure activity relationship will be discussed along with a brief introduction to the established methodologies.

Aim To observe the modulation of adenosine triphosphate (ATP) on motility of isolated gastric smooth muscle from rat.Methods Longitudinal and circular muscle strips of rat gastric body and antrum were prepared, and the effects of ATP (0.1, 1,10,100 ?mol?L~-1 and 1 mmol?L~-1 ) on the motility of the strips were investigated. Results ATP induced a small relaxation followed by an obvious spasm in longi- tudinal muscle strips of the gastric body; when tone was raised by KCl, ATP induced a larger relaxation followed by a smaller spasm.ATP only produced contraction in circular muscle strips of the gastric body.Low concentration of ATP inhibited the contractile amplitude of the antral longitudinal strips, at the same time increased the frequency of the contraction apparently; when tone was raised by KCl, ATP produced a concentration-related relaxation.Low concentration of ATP firstly enhanced and then inhibited contractile amplitude of antral circular musle strips, while high concentration of ATP fully inhibited the motility. Conclusion We firstly reported the obvious effects of ATP on longitudinal and circular strips of rat gastric body and antrum. The effects of ATP on the four preparations were different from each other, suggesting that ATP plays an important modulatory role on motility of gastric smooth muscle of rats.

Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.