Lotti V J, Kling P, Cerino D
Eur J Pharmacol. 1982 Oct 22;84(3-4):161-7. doi: 10.1016/0014-2999(82)90198-4.
Schild plots for (-)-propranolol, timolol and IPS 339, but not penbutolol or carazolol, as antagonists of isoproterenol in the isolated, field-stimulated rat vas deferens exhibited biphasic curves indicating the presence of both high and low affinity sites for these agents in this preparation. Schild plots determined for (-)-propranolol in the presence of prazosin (0.3 micron) or using the prostatic end of the rat vas deferens yielded two similar affinity sites suggesting the lack of involvement of postsynaptic alpha 1-adrenergic mechanisms in the observed response. In the presence of Gpp(NH)p(4 micron), (-)-propranolol, timolol and IPS 339 exhibited only a single affinity site which corresponded to their high affinity site in antagonizing isoproterenol in the absence of Gpp(NH)p. Similarly, only a single high affinity site was observed for (-)-propranolol when salbutamol, rather than isoproterenol, was used as the agonist. The data suggest the two affinity sites observed with some beta-adrenergic blockers in this preparation reflects a possible action of isoproterenol and the antagonists upon two subpopulations of beta 2-adrenergic receptors, one of which is sensitive to Gpp(NH)p.
在离体的、经场刺激的大鼠输精管中，作为异丙肾上腺素拮抗剂的（-）-普萘洛尔、噻吗洛尔和IPS 339的希尔德图呈双相曲线，表明该制剂中存在这些药物的高亲和力和低亲和力位点，而喷布洛尔或咔唑洛尔则不然。在哌唑嗪（0.3微米）存在的情况下或使用大鼠输精管的前列腺端测定的（-）-普萘洛尔的希尔德图产生了两个相似的亲和力位点，这表明观察到的反应中不存在突触后α1 - 肾上腺素能机制的参与。在Gpp（NH）p（4微米）存在的情况下，（-）-普萘洛尔、噻吗洛尔和IPS 339仅表现出一个单一的亲和力位点，该位点对应于它们在不存在Gpp（NH）p时拮抗异丙肾上腺素的高亲和力位点。同样，当使用沙丁胺醇而非异丙肾上腺素作为激动剂时，（-）-普萘洛尔仅观察到一个单一的高亲和力位点。数据表明，在此制剂中用一些β - 肾上腺素能阻滞剂观察到的两个亲和力位点反映了异丙肾上腺素和拮抗剂对β2 - 肾上腺素能受体两个亚群的可能作用，其中一个亚群对Gpp（NH）p敏感。
