Höcker M, Hughes J, Fölsch U R, Schmidt W E
I. Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
Eur J Pharmacol. 1993 Sep 21;242(1):105-8. doi: 10.1016/0014-2999(93)90016-b.
The CCKB/gastrin receptor antagonist, PD 135158 (CAM 1028), surprisingly stimulates lipase release from isolated rat pancreatic acini dose dependently in a biphasic manner, with identical efficacy but lower potency compared to cholecystokinin octapeptide (CCK-8). Half-maximal stimulation occurred at 0.6 microM and maximal secretion was induced at 50 microM. Supramaximal concentrations decreased lipase release. Acinar lipase secretion in response to 25 pM CCK-8 or 1 microM CAM-1028 was abolished by 5 microM of the specific CCKA receptor antagonist loxiglumide (CR 1505), half-maximal inhibition was observed at 0.6 microM for CCK-8 and 0.4 microM for PD 135158. These data demonstrate that the CCKB/gastrin receptor antagonist, PD 135158, acts as a full agonist at the rat pancreatic CCKA receptor.
胆囊收缩素B/胃泌素受体拮抗剂PD 135158（CAM 1028）令人惊讶地以双相方式剂量依赖性地刺激分离的大鼠胰腺腺泡释放脂肪酶，与八肽胆囊收缩素（CCK-8）相比，其效力相同但效能较低。半数最大刺激浓度为0.6微摩尔，50微摩尔时诱导最大分泌。超最大浓度会降低脂肪酶释放。5微摩尔特异性CCKA受体拮抗剂洛莫司琼（CR 1505）可消除25皮摩尔CCK-8或1微摩尔CAM-1028引起的腺泡脂肪酶分泌，CCK-8在0.6微摩尔、PD 135158在0.4微摩尔时观察到半数最大抑制。这些数据表明，胆囊收缩素B/胃泌素受体拮抗剂PD 135158在大鼠胰腺CCKA受体上作为完全激动剂起作用。
