Characterization of novel splice variants of the PAC1 receptor in human neuroblastoma cells: Consequences for signaling by VIP and PACAP

Lutzomyia longipalpisSalivary Peptide Maxadilan Alters Murine Dendritic Cell Expression of CD80/86, CCR7, and Cytokine Secretion and Reprograms Dendritic Cell-Mediated Cytokine Release from Cultures Containing Allogeneic T Cells

“…There are several scenarios that may serve to explain the apparent discrepancy between our work and these authors. First, PAC1 is expressed in various isoforms (14 in all) that are represented by alternate mRNA splicing (52). The distribution of the different isoforms is dependent on tissue type.…”

Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson's disease model

“…Indeed, Lutz et al (2006) demonstrated that SH-SY5Y cells can produce cAMP in presence of VIP and they concluded that the effect was mediated by PAC1. However, they also showed that the intensity of cAMP production by VIP was related to the type of PAC1 receptor They also corroborate the data of previous studies showing that neuroprotection induced by PACAP takes place through PAC1 activation and its downstream signaling cascade involving cAMP production and PKA activation (Lutz et al, 2006;Seaborn et al, 2011). Some studies have highlighted a protective effect of VIP against neurodegeneration, which would involve activation of the VPAC1 receptor (Delgado and Ganea, 2003).…”

“…The SH-SY5Y cells, which are a human neuroblastoma cell line stably expressing constitutively the PAC1 and VPAC2 receptors but not VPAC1 (Lutz et al, 2006), were cultured in a 1:1 mixture of Ham's F12 Nutrient mixture and MEM medium supplemented with 2 mM L-glutamine, 1 mM sodium pyruvate, 100 UI/mL each of penicillin and streptomycin, and 15% FBS. All cell lines were maintained as a monolayer at 37˚C in a humidified atmosphere of 5% CO 2 /95% air and cell passages were performed by trypsinization when cells were at 80% confluence.…”

“…However, although Ac-[Phe(pI) 6 , Nle 17 ]PACAP(1-27) was a weaker agonist than PACAP38 and PACAP27, at a same concentration, its activity was between 60% to 70% that of the 38-and 27-residue isoform peptides. Interestingly, vasoactive intestinal peptide (VIP) was unable to generate cAMP from SH-SY5Y cells although this neuroblastoma cell line was previously described to constitutively express PAC1 and VPAC2 receptors (Lutz et al, 2006).…”

Alarin is a vasoactive peptide

“…One of them is the PACAPpreferring PAC1 receptor (39). Further diversity in the number of VIP/PACAP receptors occurs through alternative splicing of the PAC1 receptor gene, giving rise to a large variety of PAC1 receptor isoforms with different expression and signaling properties (40). Other examples for neuropeptide receptor genes with alternative splicing include the cholecystokinin 2 receptor, calcitonin receptor, angiotensin type 1a receptor, and the neuropeptide Y Y5 receptor (41,42).…”