Fleetwood G, Gordon J L
Br J Pharmacol. 1987 Jan;90(1):219-27. doi: 10.1111/j.1476-5381.1987.tb16843.x.
The effects of an intracoronary bolus of adenosine triphosphate (ATP), alpha, beta-methylene ATP (APCPP), beta, gamma-methylene ATP (APPCP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine on coronary tone and ventricular myocardial contraction were investigated in the perfused rat heart. Adenine nucleotides, given by bolus injection were negatively inotropic in amounts greater than 3 X 10(-7) mol. The potency order was ATP greater than ADP greater than AMP. Adenosine (less than 1 X 10(-5)mol) had no effect on ventricular myocardial contraction. Adenine nucleotides and adenosine (1 X 10(-10)-1 X 10(-7) mol) reduced coronary tone. The potency order was ATP greater than ADP greater than AMP = adenosine. The ATP analogue APPCP was less active than ATP at reducing coronary tone, and APCPP had no vasodilator effect. This suggests the presence of a P2-purinoceptor, subclass P2Y, which mediates vasodilation. ATP and ADP increased the concentration of prostacyclin (measured as 6-keto prostaglandin F1 alpha) in the perfusate, but only after injection of greater than 3 X 10(-7) mol, suggesting that the vasodilator responses to ATP and ADP were not mediated by prostacyclin. AMP and adenosine had no effect, even at 1 X 10(-5) mol. At a dose of 3 X 10(-9) mol, approximately 40% of ATP and 70% of ADP was converted to AMP and adenosine whilst passing through the heart. The amounts of AMP and adenosine formed, however, were insufficient to account for the vasodilator effects of ATP and ADP. 6 Vasodilatation mediated by AMP and adenosine was inhibited by an infusion of 8-phenyltheophylline (8-PT; 2 x 10-5 M) indicating interaction with a P1-purinoceptor. Vasodilatation induced by ATP (at doses at which AMP and adenosine had no action) was also depressed by 8-PT indicating either an action of ATP on PI-purinoceptors, or an effect of 8-PT on P2y receptors. 7 Vasodilatation induced by AMP was unaltered during an infusion of alpha,beta-methylene ADP (2 x 10-6 M, which inhibited breakdown of AMP to adenosine by 54.2 +/- 1.5%, n = 4). This suggests that AMP acted directly, and it did not require conversion to adenosine to induce vasodilatation. 8 The ATP analogues APCPP (1 x 10-9_1 x 10-8 mol) and APPCP (1 x 10-8_l x 10-7mol) increased coronary tone, as did high doses (I x 10-5 mol) ofATP and ADP, indicating the presence of an additional P2-purinoceptor, subclass P2X, mediating vasoconstriction.
在灌注大鼠心脏中，研究了冠状动脉内推注三磷酸腺苷（ATP）、α,β-亚甲基ATP（APCPP）、β,γ-亚甲基ATP（APPCP）、二磷酸腺苷（ADP）、一磷酸腺苷（AMP）和腺苷对冠状动脉张力和心室心肌收缩的影响。推注给药的嘌呤核苷酸，剂量大于3×10⁻⁷mol时具有负性肌力作用。其效力顺序为ATP＞ADP＞AMP。腺苷（小于1×10⁻⁵mol）对心室心肌收缩无影响。嘌呤核苷酸和腺苷（1×10⁻¹⁰ - 1×10⁻⁷mol）可降低冠状动脉张力。效力顺序为ATP＞ADP＞AMP = 腺苷。ATP类似物APPCP在降低冠状动脉张力方面比ATP活性低，且APCPP无血管舒张作用。这表明存在一种P2嘌呤受体，即P2Y亚类，它介导血管舒张。ATP和ADP可增加灌注液中前列环素（以6-酮前列腺素F1α衡量）的浓度，但仅在注射大于3×10⁻⁷mol后才增加，这表明ATP和ADP的血管舒张反应不是由前列环素介导的。AMP和腺苷即使在1×10⁻⁵mol时也无影响。在剂量为3×10⁻⁹mol时，约40%的ATP和70%的ADP在流经心脏时转化为AMP和腺苷。然而，生成的AMP和腺苷量不足以解释ATP和ADP的血管舒张作用。由AMP和腺苷介导的血管舒张被输注8-苯基茶碱（8-PT；2×10⁻⁵M）抑制，表明与P1嘌呤受体相互作用。ATP（在AMP和腺苷无作用的剂量下）诱导的血管舒张也被8-PT抑制，这表明要么ATP作用于P1嘌呤受体，要么8-PT作用于P2y受体。在输注α,β-亚甲基ADP（2×10⁻⁶M，可使AMP向腺苷的分解抑制54.2±1.5%，n = 4）期间，AMP诱导的血管舒张未改变。这表明AMP直接起作用，且其诱导血管舒张不需要转化为腺苷。ATP类似物APCPP（1×10⁻⁹ - 1×10⁻⁸mol）和APPCP（1×10⁻⁸ - 1×10⁻⁷mol）可增加冠状动脉张力，高剂量（1×10⁻⁵mol）的ATP和ADP也如此，表明存在另一种P2嘌呤受体，即P2X亚类，介导血管收缩。
