Rand M J, Tung L H, Louis W J, Story D F
J Mol Cell Cardiol. 1986 Nov;18 Suppl 5:17-32. doi: 10.1016/s0022-2828(86)80458-8.
Postjunctional alpha-adrenoceptors subserve positive inotropic and chronotropic responses. When beta-adrenoceptors are blocked, agonists that act on alpha 1-adrenoceptors evoke positive chronotropic responses in the pithed rat and rat isolated atria. The rank order of potency for this effect is adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. The order of potency for antagonists to block the responses is prazosin greater than phentolamine greater than yohimbine. Thus, the postjunctional alpha-adrenoceptors are of the alpha 1-subtype. The positive chronotropic responses elicited by activating alpha 1-adrenoceptors have a slower time course than those elicited by activation of beta-adrenoceptors. When beta-adrenoceptors are blocked by propranolol, the positive chronotropic response to phenylephrine is enhanced by increasing the calcium concentration or by the calcium channel activator Bay K 8644 (0.1 microM), whereas the response is decreased by lowering the calcium concentration or by calcium antagonists (verapamil, nifedipine, nicardipine and diltiazem). Therefore, the positive chronotropic response to alpha 1-adrenoceptor activation involves an increased influx of calcium through calcium channels. Prejunctional alpha 1-adrenoceptors are involved in autoinhibitory feedback regulation of transmitter release from noradrenergic neurones. In rat atria, the release of noradrenaline induced by sympathetic nerve stimulation is inhibited by both clonidine and methoxamine, and is enhanced (by disruption of noradrenaline-mediated autoinhibition) by both idazoxan and prazosin. Thus, the prejunctional alpha-adrenoceptors are of both alpha 1- and alpha 2-subtypes. Drugs which produce blockade of postjunctional alpha 1-adrenoceptors could also produce an increase in neurogenic release of noradrenaline due to blockade of prejunctional alpha 1-adrenoceptors, and this might result in more complex effects than would be anticipated.
节后α-肾上腺素能受体介导正性变力性和变时性反应。当β-肾上腺素能受体被阻断时，作用于α1-肾上腺素能受体的激动剂可在脊髓横断大鼠和大鼠离体心房中引起正性变时性反应。此效应的效价顺序为肾上腺素＞去甲肾上腺素＞去氧肾上腺素＞甲氧明。拮抗剂阻断这些反应的效价顺序为哌唑嗪＞酚妥拉明＞育亨宾。因此，节后α-肾上腺素能受体为α1亚型。激活α1-肾上腺素能受体引起的正性变时性反应的时程比激活β-肾上腺素能受体引起的反应慢。当β-肾上腺素能受体被普萘洛尔阻断时，对去氧肾上腺素的正性变时性反应可通过增加钙浓度或钙通道激活剂Bay K 8644（0.1微摩尔）而增强，而通过降低钙浓度或钙拮抗剂（维拉帕米、硝苯地平、尼卡地平和地尔硫䓬）则使反应减弱。因此，对α1-肾上腺素能受体激活的正性变时性反应涉及通过钙通道的钙内流增加。节前α1-肾上腺素能受体参与去甲肾上腺素能神经元递质释放的自身抑制性反馈调节。在大鼠心房中，交感神经刺激诱导的去甲肾上腺素释放受到可乐定和甲氧明抑制，而受到咪唑克生和哌唑嗪增强（通过破坏去甲肾上腺素介导的自身抑制）。因此，节前α-肾上腺素能受体为α1和α2两种亚型。产生节后α1-肾上腺素能受体阻断作用的药物也可能由于节前α1-肾上腺素能受体阻断而导致去甲肾上腺素的神经源性释放增加，这可能导致比预期更复杂的效应。
