Ho S L, Honner V, Docherty J R
Department of Physiology, Royal College of Surgeons in Ireland, Dublin.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jun;357(6):634-9. doi: 10.1007/pl00005218.
We have investigated the subtype of alpha2-adrenoceptor mediating prejunctional inhibition of neurotransmission in rat atrium in comparison with the alpha2-adrenoceptor mediating prejunctional inhibition in rat cerebral cortex. In rat atrium and cerebral cortex, prejunctional alpha2-adrenoceptors were investigated in terms of the ability of alpha2-adrenoceptor antagonists to increase the stimulation-evoked overflow of tritium in tissues pre-incubated with [3H]-noradrenaline. The relatively non-selective alpha2-adrenoceptor antagonist yohimbine and the alpha2D-adrenoceptor selective antagonist BRL 44408 had potencies in rat atrium which were similar to their potencies in rat cerebral cortex. The antagonists ARC 239, HV 723, WB 4101, prazosin, chlorpromazine and abanoquil, which have low affinity for alpha2D-adrenoceptors, significantly increased stimulation-evoked overflow at lower concentrations in rat atrium than rat cerebral cortex. Antagonist potency at prejunctional alpha2-adrenoceptors was correlated with antagonist affinity at alpha2-adrenoceptor ligand binding sites in membranes of rat kidney (alpha2B) and submandibular gland (alpha2D), and human recombinant alpha2C-adrenoceptors labelled with [3H]yohimbine. The correlation between ligand binding sites and the functional receptor in the rat cerebral cortex was significant only for the alpha2D-adrenoceptor ligand binding site (r=0.87, n=8, P<0.01) as compared to the alpha2B-adrenoceptor (r=0.32, n.s.) or alpha2C-adrenoceptor (r=0.12, n.s.) ligand binding sites. The correlation between ligand binding sites and the functional receptor in the rat atrium was not significant for any ligand binding site, with r=0.64, 0.68 and 0.67 for the alpha2D-, the alpha2B- and the alpha2C-adrenoceptor ligand binding sites, respectively. It is concluded that the functional prejunctional alpha2-adrenoceptor of rat cerebral cortex closely resembles the alpha2D-adrenoceptor ligand binding site of rat submandibular gland, but the rat atrium may contain two subypes of prejunctional alpha2-adrenoceptor, alpha2D and another subtype, possibly alpha2B or alpha2C.
我们研究了介导大鼠心房神经传递前膜抑制的α2-肾上腺素能受体亚型，并与介导大鼠大脑皮层神经传递前膜抑制的α2-肾上腺素能受体进行了比较。在大鼠心房和大脑皮层中，通过α2-肾上腺素能受体拮抗剂增加在[3H]-去甲肾上腺素预孵育组织中刺激诱发的氚溢出的能力来研究前膜α2-肾上腺素能受体。相对非选择性的α2-肾上腺素能受体拮抗剂育亨宾和α2D-肾上腺素能受体选择性拮抗剂BRL 44408在大鼠心房中的效力与其在大鼠大脑皮层中的效力相似。对α2D-肾上腺素能受体亲和力较低的拮抗剂ARC 239、HV 723、WB 4101、哌唑嗪、氯丙嗪和阿巴诺喹，在大鼠心房中比在大鼠大脑皮层中以更低浓度就能显著增加刺激诱发的溢出。前膜α2-肾上腺素能受体处的拮抗剂效力与大鼠肾脏（α2B）和下颌下腺（α2D）膜中α2-肾上腺素能受体配体结合位点以及用[3H]育亨宾标记的人重组α2C-肾上腺素能受体处的拮抗剂亲和力相关。与α2B-肾上腺素能受体（r = 0.32，无显著性差异）或α2C-肾上腺素能受体（r = 0.12，无显著性差异）配体结合位点相比，仅α2D-肾上腺素能受体配体结合位点在大鼠大脑皮层中配体结合位点与功能受体之间的相关性显著（r = 0.87，n = 8，P < 0.01）。对于任何配体结合位点，大鼠心房中配体结合位点与功能受体之间的相关性均不显著，α2D-、α2B-和α2C-肾上腺素能受体配体结合位点的r值分别为0.64、0.68和0.67。结论是，大鼠大脑皮层功能性前膜α2-肾上腺素能受体与大鼠下颌下腺的α2D-肾上腺素能受体配体结合位点非常相似，但大鼠心房可能含有两种前膜α2-肾上腺素能受体亚型，α2D和另一种亚型，可能是α2B或α2C。
