Sneddon P, Westfall D P
J Physiol. 1984 Feb;347:561-80. doi: 10.1113/jphysiol.1984.sp015083.
The contractile response of the guinea-pig vas deferens to tetanic nerve stimulation was biphasic. The first phase was mimicked by exogenously applied ATP. The second more tonic phase was mimicked by exogenously applied noradrenaline (NA). Intracellular micro-electrodes were used to record the electrical response of the vas deferens to nerve stimulation and to exogenously applied ATP and NA. Local application of ATP (10(-5) to 10(-3)M), by pressure ejection from a micropipette, produced a depolarization similar in magnitude and time course to the excitatory junction potential (e.j.p.). NA produced no such response. Superfusion of the vas deferens with ATP and NA (10(-6) to 10(-4)M) produced a depolarization. The depolarization produced by NA was more gradual than that produced by the same concentration of ATP. The ATP-receptor antagonist ANAPP3 (arylazido aminopropionyl-ATP) preferentially antagonized the first component of the neurogenic contractile response and also antagonized the e.j.p. The alpha-receptor antagonist prazosin preferentially antagonized the second phase of the neurogenic contractile response and enhanced the e.j.p. Similar results were obtained using the irreversible alpha-receptor antagonists phenoxybenzamine and dibenamine. Cocaine (10(-6) and 10(-5)M) enhanced the second phase of the contractile response to nerve stimulation, but reduced the first phase. Lidocaine (10(-5) and 10(-4)M) had no such effect. Cocaine (10(-6) and 10(-5)M) reduced the magnitude of e.j.p.s. at all stimulation frequencies from 1 to 8 Hz. In the presence of the selective alpha 2-receptor antagonist yohimbine (10(-7)M), both phases of the contractile response to nerve stimulation were enhanced to the same degree. This concentration of yohimbine also increased the magnitude of e.j.p.s. In the presence of 10(-7) M-yohimbine, cocaine (10(-6) and 10(-5)M) still enhanced the second phase of the contractile response, but no longer reduced the initial phase of the contraction or e.j.p.s to the same degree. In vas deferens from animals pre-treated with reserpine (2 mg/kg.day), the second phase of the contractile response to nerve stimulation was reduced but neither the first phase of the contraction nor the e.j.p.s was blocked. These results suggest that the first phase of the neurogenic contractile response of the vas deferens and the e.j.p. are mediated by ATP acting on P2-purinoreceptors, whereas NA mediates phase two, via alpha 1-adrenoceptors. The results also suggest that release of ATP and NA is influenced by a negative feed-back mechanism involving presynaptic alpha 2-adrenoceptors.
豚鼠输精管对强直神经刺激的收缩反应呈双相性。第一相可被外源性应用的ATP模拟。第二相更具持续性，可被外源性应用的去甲肾上腺素（NA）模拟。使用细胞内微电极记录输精管对神经刺激以及外源性应用ATP和NA的电反应。通过微量移液器压力喷射局部应用ATP（10⁻⁵至10⁻³M），产生的去极化在幅度和时间进程上与兴奋性接头电位（e.j.p.）相似。NA未产生此类反应。用ATP和NA（10⁻⁶至10⁻⁴M）对输精管进行灌流可产生去极化。NA产生的去极化比相同浓度ATP产生的去极化更为缓慢。ATP受体拮抗剂ANAPP3（芳基叠氮氨基丙酰 - ATP）优先拮抗神经源性收缩反应的第一成分，也拮抗e.j.p.。α受体拮抗剂哌唑嗪优先拮抗神经源性收缩反应的第二相，并增强e.j.p.。使用不可逆的α受体拮抗剂酚苄明和双苄明也获得了类似结果。可卡因（10⁻⁶和10⁻⁵M）增强了对神经刺激的收缩反应的第二相，但降低了第一相。利多卡因（10⁻⁵和10⁻⁴M）无此作用。可卡因（10⁻⁶和10⁻⁵M）在1至8Hz的所有刺激频率下均降低了e.j.p.的幅度。在选择性α₂受体拮抗剂育亨宾（10⁻⁷M）存在的情况下，对神经刺激的收缩反应的两个相均以相同程度增强。该浓度的育亨宾也增加了e.j.p.的幅度。在10⁻⁷M育亨宾存在的情况下，可卡因（10⁻⁶和10⁻⁵M）仍增强收缩反应的第二相，但不再以相同程度降低收缩的初始相或e.j.p.。在经利血平（2mg/kg·天）预处理的动物的输精管中，对神经刺激的收缩反应的第二相降低，但收缩的第一相和e.j.p.均未被阻断。这些结果表明，输精管神经源性收缩反应的第一相和e.j.p.是由ATP作用于P2 - 嘌呤受体介导的，而NA通过α₁ - 肾上腺素能受体介导第二相。结果还表明，ATP和NA的释放受涉及突触前α₂ - 肾上腺素能受体的负反馈机制影响。
