Chronic elevation of cAMP levels induces changes in the adenylate cyclase system, opiate receptor sensitivity and levels of Gs-mRNA in cultured neurons.
Neurons in primary culture were treated (5 days) with the adenylate cyclase stimulator 10(-5) M forskolin. The basal adenylate cyclase was decreased by 57%. The acute stimulatory effect of forskolin was down-regulated by 48%. The inhibitory effects of the 3 opiate receptor agonists (mu, delta and kappa) were partly abolished. The abundance of mRNA encoding the stimulatory G-protein (Gs) was decreased prominently. The data indicate that the cAMP system in neuronal cells in primary culture is under dynamic regulation, possibly including altered Gs-protein gene expression. Furthermore, long-term forskolin treatment might induce increased proliferation in susceptible neural blast cells.
Eriksson
P S
PS
Institute of Neurobiology, University of Göteborg, Sweden.
Nilsson
M
M
Carlsson
B
B
Isaksson
O G
OG
Rönnbäck
L
L
Hansson
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D005333:Fetus; D019204:GTP-Binding Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*
D012333:RNA, Messenger; D011957:Receptors, Opioid; D005576:Colforsin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases