In this study receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) were characterized in chick cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]-VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding sites with high affinity (Kd = 0.21 nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 >> VIP6-28 (mammalian) > PHI (porcine) >> neurotensin6-11-chicken VIP7-28 > neurotensin6-11-mammalian VIP7-28 >>> VIP16-28 (chicken; inactive) approximately secretin (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded that the cerebral cortex of chick, in addition to PAC1 receptors, contains a population of VPAC-type receptors.
New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitor cells (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion. Gene array and reconstitution assays indicate that this effect can be attributed to the regulation of ECM components and ECM-modifying enzymes in aNPCs by PACAP. Our work suggests that PACAP regulates a bidirectional interaction between the aNPCs and their niche: PACAP modifies ECM production and remodeling, in turn the ECM regulates progenitor cell adherence. We speculate that PACAP may in this manner help restrict adult neural progenitors to the stem cell niche in vivo, with potential significance for aNPC function in physiological and pathological states.
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