alpha-MSH changes cyclic AMP levels in rat brain slices by an interaction with the D1 dopamine receptor.
The exposure of rat brain slices containing caudate putamen and accumbens nuclei to alpha-MSH or dopamine (DA) results in an increase in cyclic AMP (cAMP) levels. When tissues are compared with those containing both alpha-MSH and DA, a reduction in the cyclic nucleotide is observable. This study was carried out to determine whether variations in tissular cAMP levels induced by alpha-MSH might be explained by an interaction between the peptide and some dopaminergic receptors. Therefore, we measured cAMP in tissues and medium in response to alpha-MSH in the presence of haloperidol, the selective D1 (SCH 23390) or D2 (sulpiride) antagonists, or the selective D1 (SKF 38393) or D2 (bromocriptine) agonists. Haloperidol by itself induced no changes either in the cAMP content or in the cAMP efflux to the medium. When slices were exposed to alpha-MSH and haloperidol, the latter blocked the alpha-MSH effect of inducing an increase in the content of cAMP. None of the specific antagonists (at the administered doses) induced changes in the content of cAMP when compared with the control group. The presence of SCH 23390 in the incubation medium together with alpha-MSH yielded a reduction in cAMP levels compared with those incubated with alpha-MSH. A slight stimulatory effect on cAMP formation was observed when the dopaminergic agonists (SKF 38393 10 microM) were used. We conclude that alpha-MSH interacts with the D1 dopamine receptor, changing the cAMP levels in striatum and accumbens nuclei.
Lezcano
N E
NE
Department of Pharmacology, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Argentina.
De Barioglio
S R
SR
Celis
M E
ME
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D000242:Cyclic AMP / Q000032:analysis*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects; D011699:Putamen / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D000521:alpha-MSH; D000242:Cyclic AMP; D006220:Haloperidol