PACAP (6-38), human, ovine, rat TFA is a non-stimulatory competitive antagonist of pituitary adenylate cyclase-activating polypeptide (PACAP) with a Ki value of 2nM[1]. PACAP (6-38) acts on PACAP type I receptor, PACAP type II receptor VIP1 and PACAP type II receptor VIP2 with IC50 values of 30nM, 600nM and 40nM, respectively[2]. PACAP (6-38) can be used in neuroscience research (e.g., neuroprotection, pain regulation) and metabolic disease research (e.g., insulin secretion regulation)[3]. PACAP(6-38) can inhibit neuropeptide release from isolated tracheal sensory nerve endings[4].
In vitro, treatment of rat trigeminal ganglion cell cultures with PACAP (6-38) (1μM) for 6h induced transcriptome changes in the cells, resulting in a significant downregulation of NADH:ubiquinone oxidoreductase subunit B6 and a significant upregulation of transient receptor potential cation channel subfamily M member 8[5].
In vivo, PACAP (6-38) (0.3, 0.6, 3nM) injected intracerebroventricularly into SD mice blocked the reduction in solid food intake induced by cocaine and amphetamine regulated transcript (CARTp)[6]. PACAP (6-38) (300nM) injected intravesically into NGF-OE mice reduced baseline bladder pressure and pelvic sensitivity, but had no effect on bladder function in WT mice[7].
References:
[1] Fishbein V A, Coy D H, Hocart S J, et al. A chimeric VIP-PACAP analogue but not VIP pseudopeptides function as VIP receptor antagonists[J]. Peptides, 1994, 15(1): 95-100.
[2] Gourlet P, Vandermeers A, Vandermeers-Piret M C, et al. Fragments of pituitary adenylate cyclase activating polypeptide discriminate between type I and II recombinant receptors[J]. European journal of pharmacology, 1995, 287(1): 7-11.
[3] Toth D, Szabo E, Tamas A, et al. Protective effects of PACAP in peripheral organs[J]. Frontiers in Endocrinology, 2020, 11: 377.
[4] Nemeth J, Reglödi D, Pozsgai G, et al. Effect of pituitary adenylate cyclase activating polypeptide-38 on sensory neuropeptide release and neurogenic inflammation in rats and mice[J]. Neuroscience, 2006, 143(1): 223-230.
[5] Takács-Lovász K, Kun J, Aczél T, et al. PACAP-38 induces transcriptomic changes in rat trigeminal ganglion cells related to neuroinflammation and altered mitochondrial function presumably via PAC1/VPAC2 receptor-independent mechanism[J]. International Journal of Molecular Sciences, 2022, 23(4): 2120.
[6] Burgos J R, Iresjö B M, Smedh U. Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine-and amphetamine-regulated transcript Peptide-induced hypophagia in rats[J]. PloS one, 2013, 8(8): e72347.
[7] Girard B M, Malley S E, Mathews M M, et al. Intravesical PAC1 receptor antagonist, PACAP (6–38), reduces urinary bladder frequency and pelvic sensitivity in NGF-OE mice[J]. Journal of Molecular Neuroscience, 2016, 59(2): 290-299.
PACAP (6-38), human, ovine, rat TFA是垂体腺苷酸环化酶激活多肽（PACAP）的非刺激性竞争性拮抗剂，Ki值为2nM[1]。PACAP (6-38)作用于PACAP I型受体、 PACAP II型受体VIP1和PACAP II型受体VIP2，IC50分别为30nM、600nM和40nM[2]。PACAP (6-38)能够用于神经科学研究（如神经保护、痛觉调控）和代谢性疾病研究（如胰岛素分泌调控）[3]。PACAP(6-38)能够抑制分离气管感觉神经末梢的神经肽释放[4]。
在体外，PACAP (6-38)（1μM）处理大鼠三叉神经节细胞培养物6h，诱导了细胞的转录组变化，导致NADH：泛醌氧化还原酶亚基B6显著下调，并导致瞬时受体电位阳离子通道亚家族M成员8显著上调[5]。
在体内，PACAP (6-38)（0.3, 0.6, 3nM）通过脑室内注射处理SD鼠，阻断了可卡因和苯丙胺调节转录肽（CARTp）引起的固体食物摄入量减少[6]。PACAP (6-38)（300nM）通过膀胱内给药处理NGF-OE小鼠，降低了小鼠的基线膀胱压和盆腔敏感性，对WT小鼠的膀胱功能没有影响[7]。