Dopamine D2 receptor stimulation alters G-protein expression in rat pituitary intermediate lobe melanotropes

Abstract

Stimulation of dopamine D2 receptors inhibits melanotrope pro-opiomelanocortin (POMC) biosynthesis and alpha-melanocyte-stimulating hormone (MSH) secretion. These effects are mediated by G-protein alpha i- and alpha o-subunits and are reversed by stimulating receptors linked to activation of G alpha s protein. Melanotrope activity is increased by haloperidol, a D2 receptor antagonist, and decreased by bromocriptine, a D2 receptor agonist. Both the short and long isoforms of the D2 receptor mRNA and protein increase following chronic haloperidol treatment. After chronic bromocriptine treatment the short isoform is downregulated, whereas the long isoform is upregulated. Our hypothesis is that specific G protein alpha- subunits alter in pattern of expression similarly to the receptor isoforms. Using immunohistochemistry and in situ hybridization, this study examined changes in G alpha i, G alpha o, and G alpha s protein and mRNA expression following chronic treatments with bromocriptine or haloperidol. G alpha i3 and G alpha o immunoreactivities increased following bromocriptine treatment, whereas G alpha s and G alpha i1/2 did not change. Gs immunoreactivity increased after haloperidol treatment, whereas G alpha i1/2, G alpha i3, and G alpha o did not change. G alpha i and G alpha o mRNA increased following bromocriptine and decreased following haloperidol treatments, whereas the inverse results were observed with G alpha s mRNA. These results suggest D2 receptor activation can specifically increase G alpha i3 and G alpha o expression, and D2 receptor blockade increases G alpha s expression.