PACAP (6-38), human, ovine, rat

PACAP (6-38), human, ovine, rat is a potent PACAP receptor antagonist with IC₅₀s of 30, 600, and 40 nM for PACAP type I receptor, PACAP type II receptor VIP₁, and PACAP type II receptor VIP₂, respectively. IC50 & Target:IC50: 30 nM (PACAP type I receptor), 600 nM (PACAP type II receptor VIP₁), 40 nM (PACAP type II receptor VIP₂)^[1] In Vitro: An increase of dopamine (DA) content by HPLC analysis and/or cell proliferation identified by MTT assay by Dexamethasone (DEX) is also observed which can be inhibited by PACAP (6-38) at concentration sufficient to block PACAP type 1 (PAC1) receptor. Pretreatment with PAC1 receptor antagonist PACAP (6-38) at 0.1 or 1 μM for 2 h significantly blocks this increase of DA content by 1 μM DEX. The MTT assay shows that DEX increases cell proliferation. Moreover, this action is also inhibited by the pre-incubation of PACAP (6-38). PACAP (6-38) at 1μM shows no effect on DA content and cell proliferation for 24 h. However, PACAP (6-38) at 0.3 μM has been mentioned to reduce the spontaneous tyrosine hydroxylase (TH) accumulation in differentiated retinal cultured cells for 5 days^[2]. In Vivo: Intravesical administration of the PAC1 receptor antagonist, PACAP (6-38) (300 nM), significantly (p≤0.01) increases intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP (6-38) also decreases baseline bladder pressure in NGF-OE mice. Intravesical administration of PACAP (6-38) (300 nM) significantly (p≤0.01) reduces pelvic sensitivity in NGF-OE mice but is without effect in WT mice^[3].