Inhibition of adenylyl cyclase activity by the cholecystokinin analog SNF 9007 in neuroblastoma × glioma NG108-15 hybrid cells

• Published in: Regulatory peptides 1996, Vol.61 (1), p.51-56
• Main Authors: Roerig, Sandra C., Williams, Cynthia L., Hruby, Victor J., Burks, Thomas F., Rosenfeld, Gary C.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cyclic adenosine monophosphate (cAMP); Delta opioid receptor; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Opioid; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Second messenger
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/0167-0115(95)00137-9

The effect of the cholecystokinin B (CCK B) receptor-selective cholecystokinin octapeptide (CCK-8) analog SNF 9007 on forskolinstimulated adenylyl cyclase activity in NG108-15 hybrid cells was measured. The activity of SNF 9007 was compared to the δ opioid agonists d-Pen 2 d-Pen 5-enkephalin (DPDPE, δ 1 receptor-selective) and Tyr d-AlaPheGluValValGlyNH 2, ( d-Ala 2-deltorphin II, δ 2-receptor-selective) because SNF 9007 binds with moderate affinity to δ opioid receptors. SNF 9007 inhibited forskolin-stimulated adenylyl cyclase activity with efficacy similar to DPDPE. IC 50 determinations showed that d-Ala 2-deltorphin II was the most potent, followed by DPDPE, then SNF 9007 (IC 50 values = 0.013, 0.21 and 4.8 μM, respectively). CCK-8 had no effect on adenylyl cyclase activity. The δ 1 receptor-selective antagonist 7-benzylidenenaltrexone hydrochloride (BNTX, 10 nM) had no effect on the activity of any of these agonists, but the δ 2 receptor-selective antagonist naltriben methanesulfonate (NTB, 10 nM) increased IC 50 values of all the agonists. Combinations of BNTX and NTB (10 nM each) increased the d-Ala 2-deltorphin II IC 50 value 12-fold, the DPDPE IC 50 value 18-fold and the SNF 9007 IC 50 value 26-fold. The effect of the combined δ antagonists on SNF 9007 activity was different from the effect on DPDPE or d-Ala 2-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.