International journal of molecular medicine
-
Orexin A and B are hypothalamic peptides that act through two subtypes of receptors named OX1-R and OX2-R. The OX1-R almost exclusively binds orexin-A, whereas OX2-R is non-selective for both orexins. We previously found that rat adrenocortical cells express both orexin-receptor subtypes, and orexin-A stimulates corticosterone secretion from dispersed adrenocortical cells acting via the OX1-R. ⋯ The proliferogenic effect of orexin-A in the presence of OX2-R immuno-blockade was abrogated by the MAPK p42/p44 inhibitor PD-98059, while the antiproliferogenic effect of orexin-A in the presence of OX1-R immuno-blockade was annulled by the MAPK p38 inhibitor SB-203580. Neither inhibitor altered per se the basal PR of cultured cells. Taken together, our present findings allow us to conclude that i) orexins modulate the growth of rat adrenocortical cells cultured in vitro, by exerting both proliferogenic and antiproliferogenic effects, which are mediated by OX1-Rs and OX2-Rs, respectively; and ii) OX1-R and OX2-R growth effects involve the activation of the MAPK p42/p44 and p38 signaling cascades, respectively.