Miyahara H, Suzuki H
Br J Pharmacol. 1985 Oct;86(2):405-16. doi: 10.1111/j.1476-5381.1985.tb08910.x.
In the perfused rabbit ear artery the basal outflows of noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DOPEG) were less than 1 ng g-1 and 1-2 ng g-1 wet weight of tissue respectively. Field stimulation increased outflows of NA and DOPEG in a frequency-dependent manner, and they reached the maximum value at frequencies over 5 Hz. Tyramine (1 X 10(-6) -1 X 10(-4) M) increased basal outflow of NA and DOPEG, in a dose-dependent manner. This effect was not blocked by tetrodotoxin (TTX, 3 X 10(-7) M), but was prevented by pretreatment with 6-hydroxydopamine (6-OHDA). Tyramine increased the field stimulation-induced outflow of NA but not that of DOPEG in a dose-dependent manner. Cocaine (1 X 10(-5) M) reduced the increased outflow of NA induced by tyramine at rest and during field stimulation, without modifying DOPEG-outflow. Guanethidine (5 X 10(-6) M), increased outflows of NA and DOPEG at rest, and reduced the NA outflow induced by field stimulation. Pretreatment with guanethidine (5 X 10(-6) M) did not block the action of tyramine on NA and DOPEG basal outflows. Additional application of guanethidine during the presence of tyramine did reduce the outflow of NA induced by field stimulation, but did not modify the outflow of NA and DOPEG at rest. Tyramine at concentrations over 1 X 10(-5) M depolarized the smooth muscle membrane of the rabbit ear artery. After chemical denervation with 6-hydroxydopamine (6-OHDA) the depolarizing action of tyramine was reduced. Tyramine-induced depolarization was attenuated by prazosin (5 X 10(-6) M) or phentolamine (5 X 10(-6) M), but not by guanethidine (5 X 10(-6) M). In 6-OHDA-denervated tissues, tyramine-induced depolarization was attenuated by phentolamine but not by prazosin. Field stimulation evoked excitatory junction potential (e.j.p.), slow depolarization and spike potential in the rabbit ear artery. Tyramine reduced, while guanethidine blocked these electrical responses. Tyramine did not alter the facilitation process of e.j.ps. In tissues pretreated with guanethidine, tyramine evoked either no electrical response or a slow depolarization during field stimulation. The slow depolarization was blocked by prazosin. Tyramine reduced the NA content of tissues in a dose-dependent manner (by 31% at 10(-4) M). Guanethidine (5 X 10(-6) M) reduced the NA content by 20%. 10 We conclude that in the rabbit ear artery, tyramine depolarizes the smooth muscle membrane indirectly by releasing neuronal NA which acts on alpha-adrenoceptors, and directly by an action on the smooth muscle cells. Two NA compartments (guanethidine-sensitive and tyramine-sensitive NA) could be identified. Field stimulation releases the former with associated generation of ej.p. and slow depolarization whilst the release of the latter is not accompanied by ej.p. generation.
在灌注的兔耳动脉中，去甲肾上腺素（NA）和3,4 - 二羟基苯乙二醇（DOPEG）的基础流出量分别低于每克组织湿重1 ng和1 - 2 ng。场刺激以频率依赖性方式增加NA和DOPEG的流出量，并且在频率超过5 Hz时达到最大值。酪胺（1×10⁻⁶ - 1×10⁻⁴ M）以剂量依赖性方式增加NA和DOPEG的基础流出量。这种效应未被河豚毒素（TTX，3×10⁻⁷ M）阻断，但预先用6 - 羟基多巴胺（6 - OHDA）处理可阻止该效应。酪胺以剂量依赖性方式增加场刺激诱导的NA流出量，但不增加DOPEG的流出量。可卡因（1×10⁻⁵ M）减少了酪胺在静息和场刺激期间诱导的NA流出量增加，而不改变DOPEG流出量。胍乙啶（5×10⁻⁶ M）在静息时增加NA和DOPEG的流出量，并减少场刺激诱导的NA流出量。预先用胍乙啶（5×10⁻⁶ M）处理并未阻断酪胺对NA和DOPEG基础流出量的作用。在酪胺存在期间额外应用胍乙啶确实减少了场刺激诱导的NA流出量，但未改变静息时NA和DOPEG的流出量。浓度超过1×10⁻⁵ M的酪胺使兔耳动脉平滑肌膜去极化。用6 - 羟基多巴胺（6 - OHDA）进行化学去神经支配后，酪胺的去极化作用减弱。酪胺诱导的去极化被哌唑嗪（5×10⁻⁶ M）或酚妥拉明（5×10⁻⁶ M）减弱，但未被胍乙啶（5×10⁻⁶ M）减弱。在6 - OHDA去神经支配的组织中，酪胺诱导的去极化被酚妥拉明减弱，但未被哌唑嗪减弱。场刺激在兔耳动脉中诱发兴奋性接头电位（e.j.p.）、缓慢去极化和动作电位。酪胺使其降低，而胍乙啶阻断这些电反应。酪胺未改变e.j.p.s的易化过程。在用胍乙啶预处理的组织中，酪胺在进行场刺激时要么不诱发电反应，要么诱发缓慢去极化。缓慢去极化被哌唑嗪阻断。酪胺以剂量依赖性方式降低组织中的NA含量（在10⁻⁴ M时降低31%）。胍乙啶（5×10⁻⁶ M）使NA含量降低20%。我们得出结论，在兔耳动脉中，酪胺通过释放作用于α - 肾上腺素能受体的神经元NA间接使平滑肌膜去极化，并通过直接作用于平滑肌细胞使其去极化。可以识别出两个NA池（对胍乙啶敏感的NA和对酪胺敏感的NA）。场刺激释放前者并伴有e.j.p.和缓慢去极化的产生，而后者的释放不伴有e.j.p.产生。
