title: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) stimulate interleukin-6 production through the third subtype of PACAP/VIP receptor in rat bone marrow-derived stromal cells.
abstract: Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-derived stromal cells by neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of PACAP, PACAP-27 and PACAP-38, as well as VIP significantly increased IL-6 production by rat BM-derived stromal cells at physiological concentrations ranging from 10(-10)-10(-8) M. The three related peptides (PACAP-27, -38, and VIP) stimulated the production of both cAMP and inositol 1,4,5-trisphosphate (IP3) in rat BM-derived stromal cells with similar 50% effective concentrations. The stimulatory potency of the three related peptides for the production of IL-6, cAMP, and IP3 was almost consistent, suggesting that the dual signaling transduction pathways may be involved in PACAP/VIP-induced IL-6 production in rat BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP receptor (PVR3) was found to be abundantly expressed in both BM-derived stromal cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2 (PVR2) was detected. Furthermore, the mRNAs for PACAP and VIP were detected in the BM tissue, suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in the BM. The results shown in this paper suggest that PACAP/VIP and their receptor play an important role in the IL-6 production and perhaps in the hematopoiesis in the BM.
authors.affiliation: Institute for Animal Experimentation, University of Tokushima School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: X
authors.initials: X
authors.lastname: Xin
authors.forename: G J
authors.initials: GJ
authors.lastname: Shim
authors.forename: Y
authors.initials: Y
authors.lastname: Mokuno
authors.forename: H
authors.initials: H
authors.lastname: Uehara
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Agui
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000145:classification / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000145:classification / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: C495403:Adcyap1 protein, rat; D017931:DNA Primers; D015850:Interleukin-6; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP