Effects of alpha-MSH and cholinergic agents on cGMP and IP3 levels in rat brain slices

On one hand, it has been demonstrated that the exposure of rat brain slices containing caudate putamen and accumbens nuclei to alpha-MSH brings about an increase in cAMP. This increase is affected when dopamine is present in the incubation medium. On the other hand, an interaction of melanotropinergic-like peptides with acetylcholinergic drugs has been showed to be similar to the one observed with dopamine. In this study we have intended to measure cGMP or IP3 in response to alpha-MSH, and also to study the interaction with cholinergic drugs by measuring the second messengers recently mentioned. cGMP and IP3 have been measured in tissues and medium in their response to the effect of alpha-MSH alone or in the presence of the peptide plus pilocarpine (selective muscarinic agonist) or atropine (selective muscarinic antagonist). None of them modified the cGMP levels when compared with the control group. The exposure of rat brain slices containing CP and Acc nuclei to alpha-MSH resulted in an increase in IP3 levels. Pilocarpine by itself brought about an increase of IP3 only when the highest doses was used. Atropine did not modify the IP3 content. However, when slices were exposured to both alpha-MSH and pilocarpine, IP3 content was similar to control values. The blockage of the muscarinic receptor with atropine blocked the IP3 increase induced by alpha-MSH as well. Therefore, we assume that alpha-MSH does not induce changes in cGMP but it does change the IP3 levels, probably acting at the muscarinic receptor level.