Resumo

FIGUEIRA, Leticia  e  ISRAEL, Anita. Adrenomedullin signalling in rat cerebellar vermis. AVFT [online]. 2014, vol.33, n.3, pp.88-97. ISSN 0798-0264.

Adrenomedullin (AM) is a ubiquitous peptide. In brain, AM is expressed in several localized regions, including the cerebellum. AM signals through several pathways. Little is known about the signaling pathways associated to AM receptor in cerebellum. Therefore, we assessed the signaling pathways mediating AM action in rat cerebellum vermis, as well the receptor involved. For this purpose, male Sprague Dawley rats were sacrificed, the cerebellar vermis was dissected under stereomicroscopic control and the tissue was stimulated in vitro with AM, in the presence or absence of specific blockers of AM receptor subtypes: AM_22-52 or CGRP_8-37. ERK activation was assayed by western blot. inositol monophosphate (Ins1), cGMP and cAMP accumulation was determined by radioimmunoassay. NO was determined spectrophotometrically. Our findings demonstrate that in cerebellum, AM increased cAMP and cGMP production, NO accumulation and ERK activation. These effects are mediated through the activation of AM₁ receptor, since AM_22-52 blunted AM action, meanwhile AM increase of cAMP production is also mediated through stimulation of AM2 and CGRP receptors. These results indicate that in cerebellum AM excets its effects through several signaling pathways such NO/cGMP, AC/cAMP and/ or ERK suggesting the presence of a functional adrenomedullinergic system in cerebellum.

Palavras-chave : AM; cerebellum; signaling pathways.