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 effects of ?,?-methylene ATP ( ?,?-MeATP) on the P2X1 purino-ceptor-mediated vasoconstriction by different administration ways in the rat mesenteric artery. Methods Isometric vasoconstrictive responses to ?,?-MeATP,administered in non-accumulative manner or single concentration manner,were recorded in the rat isolated mesenteric arterial rings. Results ?,?-MeATP ( 10 -7 ～ 10 -4 mol ? L -1 ) administered in both of the two manners produced concentration-dependent vasocon-strictive responses in the rat isolated mesenteric artery. The vasoconstrictive responses to ?,?-MeATP in single-concentration administration group were greater than those in non-accumulative administration group when the vasoconstriction was standardized either by tissue wet weight or by maximal response to 120 mmol ?L-1 KCl ( P

This report indroduces the characterization of tetrodotoxin (TTX),and its pharmacological and clinical actions.

P 2 purinoceptors were first subdivided into P 2X and P 2Y subtypes, and later this classification was broadened to include P 2T , P 2Z and P 2D subtypes. In the 1990s, a new kind of receptors was found, which respond to UTP, ATP and ATP?S, but not to 2 MeSATP or ?,? MeATP, this finding led to the definition of the so called “P 2U ” or “nucleotide” receptor. Most recent evidence demonstrated the existence of a pyrimidine receptor responding to UTP but not to ATP. For this case, IUPHAR (International Union of Pharmacology) committee recommended that P 2 purinoceptors be subdivided into P2X and P2Y subtypes, any subtypes of intrinsic ion channel be termed P2Xn, and any subtypes of G protein coupled receptor be termed P2Yn purinoceptors. With the development and application of the molecular biologic technique and the cloning and expression of the receptors, the classification was strongly confirmed.

I 2 Imidazoline binding sites have been shown to exist on cardiac myocytes of human beings and rat. Both of I 1 and I 2 imidazoline binding sites have been identified on vascular smooth muscle cells of various species. Vascular I 2 imidazoline binding sites may participate in vascular smooth muscle proliferation. The sympathetic nerves supplying the cardiovascular system are endowed with presynaptic inhibitory imidazoline receptors. Being different from most of the imidazolines, moxonidine does not activate presynaptic imidazoline receptors, but SR141716A, which is considered as a selective antagonist at cannabinoid receptors, antagonizes presynaptic imidazoline receptors. It has been shown that imidazolines exhibit antiarrhythmic action. Agamatine, which is endogenous ligand at imidazoline receptors, not only decreases the rate of pacemaker firing in sinoatrial node of animal, prolongs action potential duration on cardiac myocytes of human beings and animal, but also inhibits afterdepolarizations induced by isoproterenol. On the other hand, imidazolines and guanidines inhibit the cardiovascular K ATP channel in a noncompetitive manner, those effects might interfere with the cardioprotective effects of K ATP channel.

Aim To establish a model of biphasic vasoconstriction induced by electrical stimulation, and analyze effects of 1～100 nmol?L~(-1) tetrodotoxin (TTX) on the biphasic vasoconstriction in the ring preparation of the rabbit saphenous artery. Methods Isometric vasoconstriction of the rabbit saphenous arterial rings was recorded, and the sympathetic nerves of the arterial rings were activated with electrical stimulation. Results The biphasic neurogenic vasoconstriction was consistently induced by electrical stimulation (15 V,1 ms pulse duration,2～16 Hz for 32 s) in a frequency-related manner in the rabbit saphenous artery. TTX (3 nmol?L~(-1)),a neuronally selective sodium channel blocker,did not affect the first phase of vasoconstriction,but it markedly inhibited the second phase of vasoconstrictive responses to 2～16 Hz stimulation by 44 %～67 %. Increasing the concentration of TTX to 10 nmol?L~(-1), TTX inhibited the first phase of the vasocontractive responses to 4～16 Hz stimulation by 40%～57%,whereas it inhibited more than 90% of the second phase of vasoconstriction. Concentration-response curves for NA(0.01～30 ?mol?L~(-1)) were not affected by TTX (0.1 ?mol?L~(-1)), but the same concentration of TTX completely inhibited the biphasic vascular responses to electrical stimulation. The biphasic contractile responses to electrical stimulation were all abolished by guanethidine (10 ?mol?L~(-1)), but the vasoconstrictive responses to exogenous NA were not affected by it. Conclusion Biphasic vasoconstriction can be induced by electrical stimulation,and the first and the second phases of vasoconstriction are mediated by neurotransmitters released from sympathetic nerves in the rabbit isolated saphenous arterial ring preparation.

Aim To study the effects of adenosine triphosphate(ATP) on the proliferation of Chinese esophageal carcinoma Eca-109 and hepatoma SMMC-7721 cells.Methods MTT assay was used to determine the inhibition of the proliferation of the two cultured tumor cell 1ines in vitro by ATP,adenosine(ADO) and uridine triphosphate(UTP).Morphological changes of the two cell lines induced by ATP were observed under light microscope.Results ATP(0.03～0.3 mmol?L~(-1)) and ADO(0.1～0.3 mmol?L~(1)) had inhibitory effects on Eca-109 and SMMC-7721 cells concentration-dependently,and the inhibition by ATP was stronger than that by ADO in both cell lines.For Eca-109 cell line,the maximal inhibition rate of the proliferation by ATP and ADO was 86.36% and 29.88%,and the IC_(50) was 0.056 and 0.823 mmol?L~(-1),respectively.For SMMC-7721 cell line,the maximal inhibition rate of the proliferation by ATP and ADO was 82.06% and 52.84%,and the IC_(50) was 0.218 and 0.517 mmol?L~(-1),respectively.UTP had a very weak inhibitory effect on Eca-109 cell line,with the maximal inhibition rate of 18.27%,and did not significantly affect SMMC-7721 cell line.Exposed to higher concentration(0.3 mmol?L~(-1)) of ATP for 72 h,SMMC-7721 cells displayed morphological changes of apoptosis,but Eca-109 cells did not show the characteristics of apoptosis markedly.Conclusion ATP has a strong inhibitory effect on the proliferation of Eca-109 cell line,which is mainly induced by ATP per se,and a metabolite ADO also has weaker effects.For SMMC-7721 cell line,however,ATP inhibits the cell proliferation mainly via its degradation to ADO.

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

ABSTRACT Calcium homeostasis is of crucial importance for the function of cardial myocytes in normal electrical and mechanical processes. The sarcoplasmic reticular Ca-ATPase and the sar-colemmic Na/Ca exchanger contribute mainly to the steady state of calcium in the myoplasm. The Na/Ca exchanger serves as the principal calcium extrusion mechanism and regulates calcium content of the sarcoplasmic reticulum by regulating the resting [Ca2+]i level, through which the Na/Ca exchanger regulates the force of contraction sequentially. Very small calcium entry can trigger significant sarcoplasmic reticular calcium release (CICR). During the upstroke and plateau phasesof the action potential, There is evidence that indicates Ca2+ influx via the Na/Ca exchanger, and the depolarisation-induced calcium entry on Na/Ca exchange may contribute mainly to triggering intra-cellular calcium release. Na/Ca exchange should be reevaluated as a route through which Ca2+, as a triggering signal, enters cardiac myocyte during excitation-contraction coupling.