Wang Miao, Ren Lei-ming
Department of Pharmacology, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.
Yao Xue Xue Bao. 2009 May;44(5):473-9.
This study is to observe the difference in pharmacological characteristics between circular smooth muscles of rat isolated gastric body and gastric fundus, and to investigate the effects of nucleoside and nucleotide on circular smooth muscle of the rat gastric body and the involved receptors. Circular muscle strips of the rat gastric body and gastric fundus were prepared, and contractile responses to agonists were investigated with a technique of drug-receptor interaction in functional system. There was no significant difference between the circular muscle strips of the gastric body and gastric fundus in the responses to KCl, and no difference in EC50 values of contractile responses for 5-HT and His between the two kinds of preparations (P > 0.05). However, Emax values of contractile responses to 5-HT and His [(0.81 +/- 0.26) and (0.88 +/- 0.27) g] in gastric body were significantly smaller than those in gastric fundus [(2.67 +/- 0.61) and (1.90 +/- 0.68) g, P < 0.01], and EC50 value of CCh produced contractile response [(0.45 +/- 0.15) micromol x L(-1)] in gastric body was significantly higher than that in gastric fundus [(0.20 +/- 0.09) micromol x L(-1), P < 0.01]. In precontracted circular muscle strips of the gastric body, ATP (0.1-3000 micromol x L(-1)) produced only a contractile response concentration-dependently, but the same concentration of ATP induced a biphasic response (relaxation followed by a contraction) in precontracted circular muscle strips of the gastric fundus. ATP, UTP, ADP, 2-MeSATP and alpha,beta-MeATP produced contractile responses concentration-dependently in circular muscle strips of the rat gastric body. The EC50 value for 2-MeSATP [(7.2 +/- 5.2) nmol x L(-1)] was about 500 times lower than that for Ach [(3.47 +/- 1.20) micromol x L(-1)]. The rank order of potency for the contraction was 2-MeSATP>>ADP>ATP=UTP>alpha,beta-MeATP>>adenosine. The contractile responses to ATP and UTP were not significantly affected by phentolamine, propranolol, atropine or tetrodotoxin. In conclusion, there is a significant difference in pharmacological characteristics between the circular smooth muscles of the rat gastric body and gastric fundus and nucleotides might be important mediators responsible for the contraction via a specific P2Y receptor in circular smooth muscle of the rat gastric body.
本研究旨在观察大鼠离体胃体和胃底环行平滑肌药理学特性的差异,并探讨核苷和核苷酸对大鼠胃体环行平滑肌的作用及其相关受体。制备大鼠胃体和胃底的环行肌条,采用功能系统中药物 - 受体相互作用技术研究其对激动剂的收缩反应。胃体和胃底的环行肌条对氯化钾的反应无显著差异,两种制剂对5 - 羟色胺(5 - HT)和组胺(His)收缩反应的半数有效浓度(EC50)值也无差异(P>0.05)。然而,胃体对5 - HT和His收缩反应的最大效应值[(0.81±0.26)和(0.88±0.27)g]显著小于胃底[(2.67±0.61)和(1.90±0.68)g,P<0.01],胃体中乙酰胆碱(CCh)产生收缩反应的EC50值[(0.45±0.15)μmol·L⁻¹]显著高于胃底[(0.20±0.09)μmol·L⁻¹,P<0.01]。在预收缩的胃体环行肌条中,三磷酸腺苷(ATP,0.1 - 3000μmol·L⁻¹)仅产生浓度依赖性的收缩反应,但相同浓度的ATP在预收缩的胃底环行肌条中诱导出双相反应(先舒张后收缩)。ATP、三磷酸尿苷(UTP)、二磷酸腺苷(ADP)、二甲基硫代三磷酸腺苷(2 - MeSATP)和α,β - 亚甲基三磷酸腺苷(α,β - MeATP)在大鼠胃体环行肌条中产生浓度依赖性的收缩反应。2 - MeSATP的EC50值[(7.2±5.2)nmol·L⁻¹]约比乙酰胆碱[(3.47±1.20)μmol·L⁻¹]低500倍。收缩效力的顺序为2 - MeSATP>>ADP>ATP = UTP>α,β - MeATP>>腺苷。对ATP和UTP的收缩反应不受酚妥拉明、普萘洛尔、阿托品或河豚毒素的显著影响。总之,大鼠胃体和胃底环行平滑肌的药理学特性存在显著差异,核苷酸可能是通过大鼠胃体环行平滑肌中的特异性P2Y受体介导收缩的重要介质。