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Functional and molecular diversity of PACAP/VIP receptors in cortical neurons and type I astrocytes


  • Maurizio Grimaldi,

    1. Laboratory of Adaptive Systems, NINDS, National Institutes of Health, Bethesda, MD 20892, USA
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  • Sebastiano Cavallaro

    1. Institute of Bioimaging and Pathophysiology of the Central Nervous System, Italian National Research Council, Catania, Italy
    2. Oasi Institute for Research on Mental Retardation and Brain Ageing (IRCCS), Troina (EN), Italy
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: Dr Grimaldi, Laboratory of Adaptive Systems, NINDS, National Institutes of Health, Room 4 A22 BLDG. 36, 36 Convent Drive, Bethesda, MD-20892, USA.


In the present study we determined the mRNA-expression of pituitary adenylate cyclase activating polypeptide (PACAP)/vasoactive intestinal peptide (VIP) receptors in primary cultures of rat cortical neurons and type I astrocytes, and investigated the effects of PACAP38 on adenylyl cyclase, inositol phospholipid hydrolysis and intracellular calcium homeostasis. PACAP38 elicited a concentration-dependent (1 n m–100 nm) increase in inositol phosphate levels and [Ca2+]i in neurons but not in type I astrocytes. The PACAP-induced increase of intracellular calcium concentration, [Ca2+]i, was characterized by a spike, compatible with inositol trisphosphate (IP3) -induced calcium mobilization from intracellular stores, and a plateau phase, sustained by activation of capacitative calcium entry triggered by depletion of IP3-sensitive calcium stores. In the absence of extracellular calcium, only the spike phase was present while the plateau phase was clearly reduced. In addition, thapsigargin pretreatment abolished the PACAP38-induced [Ca2+]i rise. Treatment with 1 μm VIP did not affect [Ca2+]i in either neurons or type I astrocytes, clearly indicating the coupling of PAC1–HOP subtype to phospholipase-C in neurons. In addition, as previously reported, PACAP38 stimulated cAMP formation in both neurons and type I astrocytes. Using the reverse transcription polymerase chain reaction, we found mRNA-expression of PAC1 (PACAP – HOP variant) and VPAC2 in neurons, PAC1 (PACAP – R variant), VPAC1 and VPAC2 in astrocytes. These data indicate both a functional and molecular diversity of PACAP and VIP receptors in these cell types and support the view that the PAC1-HOP variant may be responsible for phospholipase-C activation and [Ca2+]i elevation in cortical neurons.