Interaction between alpha-MSH and acetylcholinergic system upon striatal cAMP and IP3 levels

The interaction between the neuropeptide alpha-MSH and the acetylcholinergi c system as reflected by changes in cAMP and inositol 1-3-5 triphosphate(IP 3)production was investigated in an in vitro model of striatal slices. The possible involvement of D-1 receptors in cholinergic and alpha-MSH- stimula ted cAMP and IP3 production in slices of rat striatum was also examined, be cause it has been demonstrated that acetylcholinergic drugs induce endogeno us dopamine release in the striatum. alpha-MSH, pilocarpine(PL) and the sel ective muscarinic M1 agonist McN-A-343 increased cAMP and IP3 striatal leve ls, effects blocked by the D-1 antagonist SCH-23390, except for the effects of alpha-MSH on IP3. The muscarinic M-2 antagonist gallamine (GL) brought about an increase in cAMP levels, an effect blocked by SCH-23390. The M-1 a ntagonist pirenzepine (Pz) induced a decrease both in cAMP and IP3 content, and the nicotinic antagonist di-hydro-beta-eritroidine(DBE) only diminishe d cAMP production. When alpha-MSH and cholinergic agents were simultaneousl y added, cAMP and IP3 levels were modified with respect to the values reach ed when these agents were added alone. An interaction between the acetylcho linergic system and alpha-MSH through M-1 and nicotinic receptors was also observed, These results suggest that the intracellular signaling pathways r elated to cAMP and IP3 production gated by alpha-MSH and these cholinergic receptors are probably related, alpha-MSH striatum cAMP IP3 muscarinic and nicotinic receptors an in vitro model. (C) 2000 Elsevier Science Inc. All r ights reserved.