TY - JOUR
T1 - Suppression of phospholipase C blocks G(i)-mediated inhibition of adenylyl cyclase activity
AU - Fan, Guo Huang
AU - Zhou, Tian Hua
AU - Zhang, Wen Bo
AU - Pei, Gang
N1 - Funding Information:
We thank Dr. Lan Ma, Dr. Li-Guang Lou, Ya-Lan Wu and Li-Zhen Jiang for technical support and helpful discussion. This work was supported by the research grants from the National Science Foundation of China (39630130 and 39625010), Chinese Academy of Sciences and German Max-Planck Society.
PY - 1998/1/12
Y1 - 1998/1/12
N2 - The potential effect of inhibition of phospholipase C on the response of G(i)-coupled receptors was investigated in neuroblastoma x glioma hybrid (NG108-15) cells. The phospholipase C specific inhibitor 1-[6-((17β-3- methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]1H-pyrrole-2,5-dione (U73122), which did not affect basal and forskolin-stimulated adenylyl cyclase activities, time- and dose-dependently blocked δ-opioid receptor-mediated inhibition of adenylyl cyclase activity, the EC50 (0.5 μM) of which was consistent with that for inhibition of bradykinin-dependent phospholipase C activation (EC50 = 1 μM). U73122 treatment also blocked functional responses of m4 muscarinic receptor and α2-adrenoceptor in NG108-15 cells and three opioid receptors (μ, δ and opioid receptor-like receptor (ORL1)) in human neuroblastoma SK-N-SH cells. 1-[6-((17β-3-Methoxyestra-1,3,5(10)- trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione (U73343), an inactive analog of U73122, did not show any effect, which suggests that the blockade by U73122 of G(i)-coupled receptor-mediated signaling is probably mediated through inhibition of phospholipase C, although a possible direct modification of G proteins can not be excluded. Furthermore, treatment with U73122 but not U73343 blocked the GTP-induced inhibition of adenylyl cyclase, indicating blockade at the level of G(i) proteins.
AB - The potential effect of inhibition of phospholipase C on the response of G(i)-coupled receptors was investigated in neuroblastoma x glioma hybrid (NG108-15) cells. The phospholipase C specific inhibitor 1-[6-((17β-3- methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]1H-pyrrole-2,5-dione (U73122), which did not affect basal and forskolin-stimulated adenylyl cyclase activities, time- and dose-dependently blocked δ-opioid receptor-mediated inhibition of adenylyl cyclase activity, the EC50 (0.5 μM) of which was consistent with that for inhibition of bradykinin-dependent phospholipase C activation (EC50 = 1 μM). U73122 treatment also blocked functional responses of m4 muscarinic receptor and α2-adrenoceptor in NG108-15 cells and three opioid receptors (μ, δ and opioid receptor-like receptor (ORL1)) in human neuroblastoma SK-N-SH cells. 1-[6-((17β-3-Methoxyestra-1,3,5(10)- trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione (U73343), an inactive analog of U73122, did not show any effect, which suggests that the blockade by U73122 of G(i)-coupled receptor-mediated signaling is probably mediated through inhibition of phospholipase C, although a possible direct modification of G proteins can not be excluded. Furthermore, treatment with U73122 but not U73343 blocked the GTP-induced inhibition of adenylyl cyclase, indicating blockade at the level of G(i) proteins.
KW - Adenylyl cyclase
KW - G protein-coupled receptor
KW - G(i) protein
KW - Phospholipase C
KW - Phospholipase C inhibitor
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U2 - 10.1016/S0014-2999(97)01477-5
DO - 10.1016/S0014-2999(97)01477-5
M3 - Article
C2 - 9543254
AN - SCOPUS:0032509751
SN - 0014-2999
VL - 341
SP - 317
EP - 322
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -