Pituitary adenylate cyclase-actviating polypeptide induces cAMP production independently from vasoactive intestinal polypeptide in osteoblast-like cells

Atsushi Suzuki, Jun Kotoyori, Yutaka Oiso, Osamu Kaozawa

Research output: Contribution to journalArticle

18 Citations (Scopus)


Pituitary adenylate cyclase-activating polypeptide (PACAP) isolated from ovine hypothalamic tissue is a novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures. In osteoblasts, the detail in intracellular signalling systems of PACAP has not yet been clarified. In this study, we investigated the effects of PACAP on cAMP accumulation, phosphoinositide hydrolysis and Ca2+ influx in osteoblast-like MC3T3-E1 cells, compared with those of vasoactive intestinal polypeptide (VIP), which shows a considerable homology with PACAP in the N-terminal sequence. PACOA stimulated cAMP accumulation in a dose-dependent manner in the range between 0.1 nM and 0.1 μM in these cells. VIP also stimulated cAMP accumulation dose-dependently between 1 nM and 0.1 μM. The effect of PACAP on cAMP accumulation (ec50 = 3 nM) was more potent than that of VIP (ec50 = 30 nM). The cAMP accumulation stimulated by a combinatiion of PACAP (3 nM) and VIP (30 nM) was additive. [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP, an antagonist for the VIP receptor which markedly inhibited the VIP-induced cAMP accumulation, had little effect on the PACAP-induced cAMP accumulation. Either PACAP or VIP had little effect on the formation of inositol phosphates and Ca2+ influx in these cells. These results strongly suggest that PACAP stimulates cAMP production via an independent binding site from VIP osteoblast-like MC3AT3-E1 cells and that PACAp has no effect on the activation of protein kinase C nor the intracellular CA2+ mobilization in these cells.

Original languageEnglish
Pages (from-to)11-16
Number of pages6
JournalCellular Signalling
Issue number1
Publication statusPublished - 01-1994
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this