Activities of cAMP-dependent protein kinase and protein kinase C are modulated by desensitized nicotinic receptors in the rat brain.
When rats were treated with different dosages of nicotine, nicotinic acetylcholine receptors (nAChRs) were observed in activated, sub-acute desensitized, acute desensitized, and chronic desensitized states. The activities of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) were assayed in the respective rat brains. The results showed that the activities of PKA and PKC could not be modified when brain nAChRs were in an activated state. However, the activities of PKA and PKC decreased when brain nAChRs were in a sub-acute state, an acute state or a chronic desensitized state induced by repeated administration of nicotine. These results suggest that desensitized nAChRs in the rat brain can inhibit the activities of PKA and PKC, which may be responsible for nicotine dependence.
Beijing Institute of Pharmcology and Toxicology, Beijing 100850, PR China.
Xiulan
X
Sun
Yue
Y
Liu
Gang
G
Hu
Hai
H
Wang
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004334:Drug Administration Schedule; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D013997:Time Factors
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C