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Functional and molecular diversity of PACAP/VIP receptors in cortical neurons and type I astrocytes
Author(s) -
Grimaldi Maurizio,
Cavallaro Sebastiano
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00693.x
Subject(s) - neuroscience , receptor , functional diversity , diversity (politics) , biology , ecology , genetics , sociology , anthropology
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 n m ) increase in inositol phosphate levels and [Ca 2+ ] i in neurons but not in type I astrocytes. The PACAP‐induced increase of intracellular calcium concentration, [Ca 2+ ] i , was characterized by a spike, compatible with inositol trisphosphate (IP 3 ) ‐induced calcium mobilization from intracellular stores, and a plateau phase, sustained by activation of capacitative calcium entry triggered by depletion of IP 3 ‐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 [Ca 2+ ] i rise. Treatment with 1 μ m VIP did not affect [Ca 2+ ] i in either neurons or type I astrocytes, clearly indicating the coupling of PAC 1 –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 PAC 1 (PACAP – HOP variant) and VPAC 2 in neurons, PAC 1 (PACAP – R variant), VPAC 1 and VPAC 2 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 PAC 1 ‐HOP variant may be responsible for phospholipase‐C activation and [Ca 2+ ] i elevation in cortical neurons.