alpha2a adrenoceptors regulate phosphorylation of microtubule-associated protein-2 in cultured cortical neurons

Adrenoceptors have been suggested to mediate neuronal development. This study revealed the expression of alpha2A adrenoceptors in the cortical plate of fetal mouse cerebral wall. The effects of alpha2A adrenoceptor on dendrite growth were investigated in primary neuronal cultures. Application of alpha2 adrenoceptor agonists, BHT 933 or UK 14304 for 24 or 72 h resulted in a 1.5-2-fold increase in dendrite lengths. This effect was blocked by alpha2 adrenergic antagonists, RX 821002 or yohimbine, as well as a alpha2A selective antagonist, BRL 44408, but not by alpha2B/alpha2C selective antagonists ARC 239, imiloxan and rauwolscine. Guanfacine, a alpha2A selective agonists, also significantly increased the dendrite lengths in culture. These results suggest that the morphological effect is wholly attributable to alpha2A adrenoceptor activation. We further tested the hypothesis that alpha2A adrenoceptors act through altering the phosphorylation state of microtubule-associated protein 2. The results showed that the phosphorylation of microtubule-associated protein 2 was significantly reduced on both serine and threonine residues by over 40% after 2 h of application of guanfacine and was maintained at this low level for a prolonged time up to 96 h. These findings suggest that alpha2A adrenoceptors regulate the phosphorylation of microtubule-associated protein 2, which in turn mediates dendrite growth of cortical neurons.