Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil.
J Neurochem. 2013 Mar;124(5):621-31. doi: 10.1111/jnc.12121. Epub 2012 Dec 28.
Pituitary Adenylyl Cyclase-Activating Polypeptide (PACAP) is a neuroactive peptide present in the avian retina where it activates adenylyl cyclase (AC) since early in development via PACAP receptors. The synthesis of cAMP in response to PACAP is observed since embryonic day 8/9 (E8/9). After E12, signaling via PACAP receptors desensitizes, reaching very low levels in the mature tissue. We show here that chronic administration of PACAP in vitro desensitizes PACAP-induced cAMP accumulation, while the administration of the PACAP antagonist (PACAP 6-38) re-sensitizes PACAP receptor/cyclase system in vitro and in vivo. Moreover, a twofold increase in the number of tyrosine hydroxylase positive (TH⁺) cells is observed after in vivo injection of PACAP6-38. NURR1, a transcription factor associated with the differentiation of dopaminergic cells in the CNS, is present in the chick retina in all developmental stages studied. The presence of NURR1 positive cells in the mature tissue far exceeds the number of TH⁺ cells, suggesting that these NURR1-positive cells might have the potential to express the dopaminergic phenotype. Our data show that if PACAP signaling is increased in mature retinas, plastic changes in dopaminergic phenotype can be achieved.
垂体腺苷酸环化酶激活肽（PACAP）是一种存在于禽类视网膜中的神经活性肽，它在早期发育过程中通过 PACAP 受体激活腺苷酸环化酶（AC）。自胚胎第 8/9 天（E8/9）起，就可以观察到对 PACAP 的 cAMP 合成反应。在 E12 之后，通过 PACAP 受体的信号转导脱敏，在成熟组织中达到非常低的水平。我们在这里表明，体外持续给予 PACAP 会使 PACAP 诱导的 cAMP 积累脱敏，而给予 PACAP 拮抗剂（PACAP 6-38）会在体外和体内重新敏化 PACAP 受体/环化酶系统。此外，在体内注射 PACAP6-38 后，观察到酪氨酸羟化酶阳性（TH⁺）细胞的数量增加了两倍。NURR1 是一种与 CNS 中多巴胺能细胞分化相关的转录因子，存在于研究的所有发育阶段的鸡视网膜中。在成熟组织中存在大量的 NURR1 阳性细胞，远远超过 TH⁺细胞的数量，这表明这些 NURR1 阳性细胞可能具有表达多巴胺能表型的潜力。我们的数据表明，如果在成熟的视网膜中增加 PACAP 信号，就可以实现多巴胺能表型的可塑性变化。
