The mu opioid agonist DAMGO stimulates cAMP production in SK-N-SH cells through a PLC-PKC-Ca++ pathway.
The mu-opioid agonist DAMGO exerts a dual activity on cAMP production in SK-N-SH neuroblastoma cells. While the classic inhibitory effect was prevented by pretreating the cells with pertussis toxin (PTX), the stimulatory activity was PTX-resistant. The stimulatory effect was abolished by the selective phospholipase C (PLC) blocker U-73122, by the selective protein kinase C (PKC) blocker chelerythrine and by the calcium-channels blockers Ni++, Co++ and Cd++. Hence, it is suggested that the opioid receptor activates PLC (probably through Gq GTP-binding proteins), to mobilize PKC, that positively modulates calcium channels in the plasma membrane; the entry of Ca++ into the cells stimulates calcium-activated adenylyl cyclases to produce cAMP.
Rubovitch
Vardit
V
The Mauerberger Chair in Neuropharmacology, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Gafni
Mikhal
M
Sarne
Yosef
Y
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D037342:Pertussis Toxin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases