D'Agata V, Cavallaro S, Stivala F, Canonico P L
Institutes of Pharmacology and General Pathology, University of Catania Medical School, 95100 Catania, Italy.
Eur J Neurosci. 1996 Feb;8(2):310-8. doi: 10.1111/j.1460-9568.1996.tb01215.x.
The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27,and PACAP38, are novel members of the vasoactive intestinal peptide (VIP)/secretin/glucagon family of peptides. PACAP receptors that are positively coupled to adenylate cyclase and phospholipase C have been recently identified. We examined the expression of PACAP receptors in the rat cortex, hippocampus, cerebellum and hypothalamus during postnatal development. Functional studies revealed PACAP stimulation of cAMP formation in all the brain areas examined and [3H]inositol monophosphate ([3H]InsP) accumulation only in the cerebellum and hypothalamus. Throughout development, the efficacy or PACAP in stimulating cAMP formation slightly increased in the cortex and hypothalamus and decreased in the hippocampus and cerebellum; PACAP stimulation of [3H]InsP formation decreased in the cerebellum and remained steady in the hypothalamus. The effects of PACAP27 and PACAP38 on cAMP levels and inositol phospholipid hydrolysis were dose-dependent between 1 and 100 nM. In the same brain areas, treatment with VIP increased cAMP formation at doses greater than 100nM and failed to affect [3H]InsP content, thus suggesting the existence of type-1 PACAP receptors. The reverse transcription polymerase chain reaction (RT-PCR) was used to analyse the mRNA expression of type-1 PACAP receptor splice variants. PACAP receptor gene expression in the central nervous system was regulated in a developmental- and tissue-specific manner. The PACAP-R transcript was detected in all the brain areas examined whereas PACAP-R-hop mRNA ocurred only in the cerebellum and hypothalamus. The different expression profiles and functional properties of PACAP receptors in the developing rat brain suggest an involvement of PACAP in histogenesis, maturation and neurotransmission.
垂体腺苷酸环化酶激活多肽的两种形式，即PACAP27和PACAP38，是血管活性肠肽（VIP）/促胰液素/胰高血糖素肽家族的新成员。最近已鉴定出与腺苷酸环化酶和磷脂酶C正偶联的PACAP受体。我们研究了出生后发育过程中大鼠皮质、海马、小脑和下丘脑PACAP受体的表达。功能研究显示，PACAP刺激了所有检测脑区的cAMP形成，而[3H]肌醇单磷酸（[3H]InsP）仅在小脑和下丘脑积累。在整个发育过程中，PACAP刺激皮质和下丘脑cAMP形成的效力略有增加，而在海马和小脑中则降低；PACAP刺激小脑[3H]InsP形成的作用降低，而在下丘脑中保持稳定。在1至100 nM之间，PACAP27和PACAP38对cAMP水平和肌醇磷脂水解的影响呈剂量依赖性。在相同脑区，大于100 nM剂量的VIP处理可增加cAMP形成，但不影响[3H]InsP含量，因此提示存在1型PACAP受体。采用逆转录聚合酶链反应（RT-PCR）分析1型PACAP受体剪接变体的mRNA表达。中枢神经系统中PACAP受体基因的表达以发育和组织特异性方式受到调控。在所检测的所有脑区均检测到PACAP-R转录本，而PACAP-R-hop mRNA仅在小脑和下丘脑出现。发育中大鼠脑内PACAP受体不同的表达谱和功能特性提示PACAP参与了组织发生、成熟和神经传递过程。
