Roerig S C, Williams C L, Hruby V J, Burks T F, Rosenfeld G C
Department of Pharmacology, Louisiana State University Medical Center, Shreveport 71130, USA.
Regul Pept. 1996 Jan 16;61(1):51-6. doi: 10.1016/0167-0115(95)00137-9.
The effect of the cholecystokininB (CCKB) receptor-selective cholecystokinin octapeptide (CCK-8) analog SNF 9007 on forskolin-stimulated adenylyl cyclase activity in NG108-15 hybrid cells was measured. The activity of SNF 9007 was compared to the delta opioid agonists D-Pen2-D-Pen5-enkephalin (DPDPE, delta 1 receptor-selective) and Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2, (D-Ala2-deltorphin II, delta 2-receptor-selective) because SNF 9007 binds with moderate affinity to delta opioid receptors. SNF 9007 inhibited forskolin-stimulated adenylyl cyclase activity with efficacy similar to DPDPE. IC50 determinations showed that D-Ala2-deltorphin II was the most potent, followed by DPDPE, then SNF 9007 (IC50 values = 0.013, 0.21 and 4.8 microM, respectively). CCK-8 had no effect on adenylyl cyclase activity. The delta 1 receptor-selective antagonist 7-benzylidenenaltrexone hydrochloride (BNTX, 10 nM) had no effect on the activity of any of these agonists, but the delta 2 receptor-selective antagonist naltriben methanesulfonate (NTB, 10 nM) increased IC50 values of all the agonists. Combinations of BNTX and NTB (10 nM each) increased the D-Ala2-deltorphin II IC50 value 12-fold, the DPDPE IC50 value 18-fold and the SNF 9007 IC50 value 26-fold. The effect of the combined delta antagonists on SNF 9007 activity was different from the effect on DPDPE or D-Ala2-deltorphin II activity. These data suggest that the interaction of the CCK-8 analog SNF 9007 with opioid receptors in NG108-15 hybrid cells is different from the interaction of opioid peptides with these receptors.
测定了胆囊收缩素B（CCKB）受体选择性八肽胆囊收缩素（CCK-8）类似物SNF 9007对福斯可林刺激的NG108-15杂交细胞中腺苷酸环化酶活性的影响。将SNF 9007的活性与δ阿片受体激动剂D-青霉胺2-D-青霉胺5-脑啡肽（DPDPE，δ1受体选择性）和酪氨酸-D-丙氨酸-苯丙氨酸-谷氨酸-缬氨酸-缬氨酸-甘氨酸-酰胺（D-丙氨酸2-δ-内啡肽II，δ2受体选择性）进行比较，因为SNF 9007与δ阿片受体具有中等亲和力。SNF 9007抑制福斯可林刺激的腺苷酸环化酶活性的效力与DPDPE相似。IC50测定表明，D-丙氨酸2-δ-内啡肽II效力最强，其次是DPDPE，然后是SNF 9007（IC50值分别为0.013、0.21和4.8微摩尔）。CCK-8对腺苷酸环化酶活性无影响。δ1受体选择性拮抗剂盐酸7-苄叉基纳曲酮（BNTX，10纳摩尔）对这些激动剂的活性均无影响，但δ2受体选择性拮抗剂甲磺酸盐纳曲本（NTB，10纳摩尔）增加了所有激动剂的IC50值。BNTX和NTB（各10纳摩尔）联合使用使D-丙氨酸2-δ-内啡肽II的IC50值增加了12倍，DPDPE的IC50值增加了18倍，SNF 9007的IC50值增加了26倍。联合使用的δ拮抗剂对SNF 9007活性的影响与对DPDPE或D-丙氨酸2-δ-内啡肽II活性的影响不同。这些数据表明，CCK-8类似物SNF 9007与NG108-15杂交细胞中阿片受体的相互作用与阿片肽与这些受体的相互作用不同。
