TY - JOUR
T1 - Inhibition of adenylyl cyclase activity by the cholecystokinin analog SNF 9007 in neuroblastoma × glioma NG108-15 hybrid cells
AU - Roerig, Sandra C.
AU - Williams, Cynthia L.
AU - Hruby, Victor J.
AU - Burks, Thomas F.
AU - Rosenfeld, Gary C.
N1 - Funding Information:
The authors appreciate the excellent technical assistance of Mr. Kurt Howse. These studies were supported by National Institutes on Drug Abuse DA07972 (S.C.R.) and DA02163 (T.F.B.).
PY - 1996/1/16
Y1 - 1996/1/16
N2 - 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 δ opioid agonists D-Pen2 - D-Pen5-enkephalin (DPDPE, δ1 receptor-selective) and Tyr - D-Ala - Phe - Glu - Val - Val - Gly - NH2, (D-Ala2-deltorphin II, δ2-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. 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 μM, respectively). CCK-8 had no effect on adenylyl cyclase activity. The δ1 receptor-selective antagonist 7-benzylidenenaltrexone hydrochloride (BNTX, 10 nM) had no effect on the activity of any of these agonists, but the δ2 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 δ 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.
AB - 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 δ opioid agonists D-Pen2 - D-Pen5-enkephalin (DPDPE, δ1 receptor-selective) and Tyr - D-Ala - Phe - Glu - Val - Val - Gly - NH2, (D-Ala2-deltorphin II, δ2-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. 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 μM, respectively). CCK-8 had no effect on adenylyl cyclase activity. The δ1 receptor-selective antagonist 7-benzylidenenaltrexone hydrochloride (BNTX, 10 nM) had no effect on the activity of any of these agonists, but the δ2 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 δ 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.
KW - Cyclic adenosine monophosphate (cAMP)
KW - Delta opioid receptor
KW - Opioid
KW - Second messenger
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U2 - 10.1016/0167-0115(95)00137-9
DO - 10.1016/0167-0115(95)00137-9
M3 - Article
C2 - 8701027
AN - SCOPUS:0030050788
SN - 0167-0115
VL - 61
SP - 51
EP - 56
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 1
ER -