Curro F A, Greenberg S
Methods Find Exp Clin Pharmacol. 1983;5(1):17-32.
The contractile responses of the canine intralobar pulmonary arteries (IPA) and dorsal metatarsal veins (DMV) to alpha adrenergic receptor agonists were evaluated in the absence and presence of alpha receptor antagonists to determine the type of post-synaptic alpha receptor predominant in the cutaneous and pulmonary canine vasculature. Rings of IPA, in vitro, contracted in response to the alpha 1 receptor agonist phenylephrine (PE), and the mixed alpha agonist norepinephrine (NE) but did not contract in response to clonidine (C), an alpha 2 receptor agonist. DMV contracted in response to each of the agonists. The contractile responses of the IPA to NE and PE were antagonized by tolazoline, phentolamine, clonidine and prazosin. The contractile responses of the DMV to clonidine were only antagonized by clonidine and phentolamine but not by tolazoline or prazosin. These data suggest that: 1) IPA are selectively endowed with post-synaptic alpha 1 adrenergic receptors; 2) DMV are endowed with both post-synaptic alpha 1 and alpha 2 adrenergic receptors; and 3) clonidine interacts with alpha 1 adrenergic receptors to elicit alpha blockade and with alpha 2 adrenergic receptors to initiate contraction of the DMV. In an attempt to verify this hypothesis, experiments were performed in solutions in which the pH was altered above or below pH 7.4. Under these conditions, the agonist properties of clonidine were selectively inhibited whereas its blocking potency was retained. These data support the conclusion that clonidine is antagonistic at alpha 1 adrenergic receptors and agonistic at alpha 2 adrenergic receptors.
在有无α受体拮抗剂的情况下,评估犬叶内肺动脉(IPA)和跖背静脉(DMV)对α肾上腺素能受体激动剂的收缩反应,以确定犬皮肤和肺血管系统中占主导地位的突触后α受体类型。体外实验中,IPA环对α1受体激动剂去氧肾上腺素(PE)和混合α激动剂去甲肾上腺素(NE)产生收缩反应,但对α2受体激动剂可乐定(C)无收缩反应。DMV对每种激动剂均产生收缩反应。IPA对NE和PE的收缩反应可被妥拉唑啉、酚妥拉明、可乐定和哌唑嗪拮抗。DMV对可乐定的收缩反应仅被可乐定和酚妥拉明拮抗,而不被妥拉唑啉或哌唑嗪拮抗。这些数据表明:1)IPA选择性地具有突触后α1肾上腺素能受体;2)DMV同时具有突触后α1和α2肾上腺素能受体;3)可乐定与α1肾上腺素能受体相互作用引发α阻断,与α2肾上腺素能受体相互作用引发DMV收缩。为验证这一假设,在pH值高于或低于7.4的溶液中进行了实验。在这些条件下,可乐定的激动剂特性被选择性抑制,而其阻断效力得以保留。这些数据支持可乐定对α1肾上腺素能受体具有拮抗作用且对α2肾上腺素能受体具有激动作用的结论。