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.